At an airport in Los Angeles, flight attendants Jenny and Paula are getting ready for their next trip. Captain Forrest and his co-pilot Willsy chat with them and they notice they won’t have many passengers tonight because of the thunderstorms. Willsy also takes some medicine because he isn’t feeling well.
Then the attendants meet tonight’s passengers. George is a teenager who always flies alone and doesn’t like to be smothered. Bev has come with her husband Doctor Kingston, whose Parkinson's doesn’t allow him to move or speak.
Army medic Shilah is nervous about flying while Louise is relaxing with her cat. Nial and Susan are expecting a baby and are quite germophobic so they clean their seats before sitting while Hvorst and Nicca are excited foreigners who don’t speak very good English. Henry has brought a cage of hamsters and when Ralph tries to help him put it in the storage bin, he gets bitten in the process.
The cage won’t fit so the flight attendants force Henry to send it to the cargo hold. Businessman Preston keeps sneezing, apparently sick with the same thing Willsy has. As the plane finally takes off, Jenny has to remind Nial to hang up his phone and when he refuses, Henry forces him to.
Both men get angry and argue, so Jenny sends them back to their seats by reminding they could be arrested when they land if they don’t behave. Afterward Henry flirts with Jenny, telling her about his PHD and making a comment about the sorry state of society’s manners. Moments later Henry is watching the news and learns that the Center for Disease Control or CDC has surrounded an apartment building in Los Angeles.
Meanwhile Ralph isn’t feeling well and asks for water while staring at the wound on his thumb. Jenny notices he’s sitting in a weird position and when she checks on him, he suddenly pukes all over her. His mouth is foaming as he demands to get off, so the flight attendants try their best to take care of him.
Nobody notices the cat sneaking around and eating some puke off the floor. Jenny leaves the guy with Paula and goes to clean all the puke off her body, but at that moment Ralph runs down the corridor and pushes her down. He starts pounding on the cockpit door, asking for the plane to stop, so Willsy follows protocol and locks the door while Forrest warns ground control of the situation.
Henry tries to stop Ralph but he’s easily overpowered, and the same happens to George. Then Preston, George, Paula, and Shilah team up with Henry to hold Ralph and eventually knock him out. Using plastic restraints, they tie up his wrists.
Afterward Shilah checks nobody was injured while Jenny freaks out in private, telling Paula how she failed to be useful in an emergency. At that moment Forrest announces he’s been given orders to land and sends everyone to their seats. The plane shakes a lot as it goes down and the attendants teach everyone to keep their heads down.
Ralph’s body keeps sliding and bumping his head, so Jenny and Paula have to make an effort to move him to a seat. While Paul struggles with the seatbelt, Ralph wakes up with red eyes and bites her nose, severely injuring her. Then Ralph goes crazy and once again the passengers have to team up to push him into the bathroom, locking him up.
As the plane finally lands, Shilah uses the emergency first aid kit to give Paul some medicine that will prevent her from going into shock and ties a scarf around her face, but she’s losing a lot of blood and needs immediate medical attention. Forrest is frustrated because ground control tells them to wait even though they know about the emergency and he decides to break the rules by choosing an unassigned gate. Thankfully baggage handler Ed sees the plane coming and opens the gate just in time.
Forrest and Willsy hold the plane's bathroom door shut while everyone else desperately leaves the plane except for Bev and Kingston because they need help moving. Ed guides the group to the other end of the gate but the door is locked and nobody answers his request on the radio. They have no choice but to follow Ed through an employee entrance to enter the staging area of the airport.
The group takes the stairs and Ed reaches the other doors, however he’s shocked to discover they’re all locked, which never happens. When he checks the power box, he confirms they’re under lockdown and everything they do will be seen on the security cameras, which are still active. An argument on what to do ensues but it’s interrupted by the sudden sound of sirens.
They look through a window and notice ambulances and police cars outside, only for the window to be covered. A voice announces that the group has been quarantined and they have to wait until help comes. The passengers call their families to tell them what’s happening before teaming up to yell at Jenny, seeing her as the representation of the airline’s decisions.
Jenny doesn’t know how to defend herself, but thankfully Shilah interrupts the yelling to point out she has a medical kit in her luggage that could help Paula survive a few more hours. Jenny takes Ed and few passengers with her to look for Shilah’s luggage, but at that moment the power goes out. Ed guides them with his flashlight and when they return to the plane, they discover Willsy and Forrest are gone.
Jenny opens the bathroom and is horrified to see blood everywhere. Preston moves to get his laptop and bumps into Kingston, who is sitting alone. His wife is gone and when the others wonder what happened, Kingston uses his eyes to point at a pair of plastic cuffs on the floor that have been chewed through.
Meanwhile Ed cuts the carpet on the floor to reach a hatch that takes them directly to the baggage hold. Jenny reaches for Shilah's medical kit while Nial grabs a gun from his suitcase. Ed freaks out when a rodent walks by his feet and scares it away while saying it was a rat, but Henry thinks it was just one of his hamsters because he’s found the broken cage.
As Jenny climbs out of the hold, she looks around and notices Preston's laptop covered with blood. At the end of the corridor, Willsy is running on his fours, growling and also covered in blood. Suddenly an infected Forrest appears behind Jenny and attacks her.
The guys immediately come out to help but punches do nothing, so Nial shoots him to death as some of Forrest’s blood falls on his face. Afterward the group runs off the plane and in the gate corridor they find Kingston thrown from his wheelchair and an unconscious Preston bitten on the back of the neck. Nearby Jenny finds Bev crying and begging for help, but she suddenly transforms and attacks as well.
Fortunately Jenny outruns her and the guys push the door to lock her out. The group goes back to the others and Shilah does her best to take care of Paula. Susan cleans the blood off Nial's face yet they still share a kiss.
Henry and Ed put furniture in front of the door to keep Bev out and Jenny looks around, finding drops of blood on the floor and worrying about where they came from. Finally snapping, Jenny tells everyone to shut up and takes over leadership since the captain is dead. Shilah explains this isn’t any known disease and Jenny remembers the building on the news, which was also quarantined.
Kingston notices a rat with very red eyes nearby but he can barely hum so he isn’t heard. The rat falls on his head and manages to bite him before George knocks it off. While the guys catch the rat in a bucket, Shilah takes care of the wound.
Then the group agrees to lock George and Paula up in a crate in case they’ll transform as well. Then Ed uses a glove to grab the rat and notices there’s a tag on its leg, meaning it escaped from a lab. George says Henry brought it and lied about the hamsters because he’s certain he saw long tails in the cage earlier.
When Henry denies it, Jenny takes him aside to demand the truth and Henry swears he didn’t, pointing out lab rats wouldn’t have passed the security check. As they hug each other for comfort, suddenly Ralph comes out and jumps on Jenny while ignoring Henry’s attempts to stop him. The others hear the screaming and rush to help, combining their strength to strangle Ralph with a hose.
At that moment Ed gets a message on the radio saying that the CDC is finally there. The group gathers at the door but the four officers come in instead of letting them out. They hold the group at gunpoint while taking the rat and Nial’s weapon, then they go to Paula and Kingston to give them injections.
The group demands an explanation but the officers only say it’s protocol. The officers then demand the others to also agree to an injection. Everyone is hesitant so Louise volunteers first, but before she can be injected her cat bites her neck and runs away.
While an officer opens fire and misses every shot, Kingston finally transforms and jumps on the guy to bite him. The other officers shoot Kingston down and try to take their partner away, only to find the door locked. They shoot at it to force it open and run outside, so Hvorst uses the chance to follow them out.
The police open fire as soon as they see them and kill them all except for one agent, who only gets shot in the leg. The group drags the surviving agent inside before closing the door. At that moment they hear the roars of the infected people getting closer so they run to hide inside a container.
Susan stops when she notices Nial foaming at the mouth, so the others have to drag her in as they explain he’s infected as well. After closing the container, Shilah points out each injection had a different color, so everyone was getting a different thing and not just “protocol”. Henry reveals he picked up a gun and forces the officer to confess what he knows.
It turns out he isn’t with the CDC, he’s actually with the CBDT or Chemical Biological Domestic Terrorism organization, which works under Homeland Security. One of their units went to that apartment in L. A.
a few hours ago but nobody came out. In the attic they found a bio-terror laboratory created by a cult. They tried to develop a cure based on a survivor but it only made it worse, implying this group was going to be the next human trial.
After confirming the rats carry the disease, the officer takes the gun from Henry and self-deletes. Nicca has a breakdown while Ed remembers this terminal often gets flooded because of an old drainage tunnel, meaning they could escape through it if they find it. Suddenly Willsy appears on an opening on top of the container and grabs Ed’s hand, so Henry tries to shoot him only to discover he has no bullets.
Ed tells George to push a button that lifts the container and crushes Willsy against a beam. Afterward the group leaves the container and Ed guides them through the area while Jenny notices Henry is missing. Nicca walks at the back and suddenly something drags her away from the others, so the group hurries up the stairs to escape.
In secret, Henry is accessing a bag with another gun. As the group runs, Jenny trips and finds Paula, who has transformed too. Jenny has to accept her friend is gone and uses a wrench to fight the creature until she pushes her off the platform, killing her.
Then the group makes it to an office where they look for the terminal blueprints, which show them a way through a wall to find the drainage tunnel. Meanwhile George reveals he stole Henry’s bag and inside he finds suspicious documents recording lab experiments, not to mention a mysterious box. At that moment Susan and Nial find them and try to attack, but Henry comes back and shoots them both just in time.
Ed notices that Henry was bitten and George uses the chance to open the box, revealing a bunch of medicine and a syringe. Henry finally admits he did bring the rats and explains he’s part of the cult mentioned by the officer. Their goal is to clean the planet from humans, who keep growing more violent and destructive every day.
Henry threatens to kill Jenny if George doesn't hand over the antidote so Ed jumps on him to stop him, only to get shot dead. The others are now scared and let Henry have the antidote, which he mixes with the blood from his wound and injects in his eye while explaining his group has followers in various organizations and that’s how he got the rats pass security. Now Henry is ready to leave and wants to bring George as hostage.
Jenny tries to stop him, but Henry knocks her down and escapes with the kid and the blueprints. Jenny is extremely dizzy so Shilah goes out first. Minutes later Jenny comes out too and is found by an infected Preston.
A chase ensues and Preston almost grabs her, so Jenny has to kick him off. Then she lures him into a machine and bashes his head with a hatch lid until he’s dead. Afterward she continues to search for George and has to take a different route when she sees a transformed Nicca standing nearby.
Going into another room she bumps into Shilah, who has retrieved the officer’s thermal goggles. She puts them on Jenny and reveals she’s been bitten, so she asks Jenny to go after George while she buys her some time. Shilah goes back to the main room and talks loudly to get the attention of the remaining infected people, who immediately jump on her to kill her.
Jenny finds a hole in the wall that Henry opened to go after the tunnel and when she’s about to get in, she’s grabbed by Louise. Using the wrench, she hits Louise until she knocks her down. Then Jenny walks through the section between walls, noticing blood drops on the ground thanks to the goggles.
She gets scared when she sees some animals, but they're just mice and not the lab rats. Following the blood trail, Jenny finds the blueprints and Henry’s shirt next to a ladder that goes into the drainage tunnel. She looks down and finds George, who explains the antidote didn’t work and Henry has transformed too.
Ignoring George’s warnings, Jenny goes down and notices some blood falling on her goggles. Suddenly Henry appears and attacks her, making her drop the goggles before he starts throwing her around. While Jenny tries her best to hold him back, George puts on the goggles and grabs the gun, shooting Henry down.
Now free, Jenny takes back the goggles and uses the wrench to finish Henry off with a blow to the head. At that moment huge flames appear down the hatch, meaning the teams outside are burning down the terminal. The exit is unfortunately blocked, but Jenny finds a baggage tunnel and kicks down the lid.
George is too scared to go down there, so Jenny gives him the goggles and allows him to go first for safety. As they hear explosions going off outside, the duo moves as fast as they can, however Jenny soon begins getting tired and realizes she’s infected. George turns around and notices her puking, yet he refuses to leave without her.
Jenny agrees to keep on following him just for his sake. Eventually they find the exit, which is blocked by bars. George manages to simply walk through them and when he turns around again, a transformed Jenny reaches through the bars to attack him.
Thankfully she’s too big to come through and George gets free by taking off his jacket. Afterward George finally gets to escape from the airport. Meanwhile Louise’s cat escapes too and makes its way to the city.
