Sam and Dean are called in to investigate when a plane crashes under mysterious circumstances, leading them to the conclusion that a demon is possessing people and causing them to crash the plane they are on.
After a plane crash with only seven survivors, including the pilot and a stewardess, Dean and Sam are called by the friend of their father Jerry Panowski, who also works in United Britannia Company and shows the last message from the cabin scrambled with an eerie voice saying "No survivors". Dean and Sam interviews a survivor in a psychiatric hospital, who believes that had seen a passenger opening the emergency exit of the plane, which would be impossible for a human being. They investigate the wrecked plane and find sulfur on the lever of the emergency exit and conclude that a fiend had possessed a passenger and caused the crash. When the surviving pilot dies in another plane crash, they track another survivor, the stewardess Amanda Walker, and convince her help them to exorcise the demon from the co-pilot of the flight.
A friend of John's calls Sam and Dean for help about a strange recording on the black box of a crashed plane. They soon realize that the demon which caused the crash is picking off the crash's only seven survivors.
- In Pennsylvania, a nervous man in an airport prepares to board a flight when a dark shadow comes in through the air vent and seems to go inside him, causing his eyes to flip momentarily black. Aboard the plane, he asks his seatmate how long they have been in the air, and when she says forty minutes, he casually gets up and opens the emergency exit door, causing the plane to crash.
Elsewhere, Sam (Jared Padalecki) awakens Dean (Jensen Ackles) early in the morning, and when Dean pressures him, he admits he hasn't been sleeping and has been suffering nightmares about Jess and about the job. Dean, on the other hand, says the job doesn't bother him. He receives a phone call from a man, Jerry, whom he and John once helped with a poltergeist. He asks for their help and they go to see him, and he explains about the plane crash and plays a recording from the cockpit, including strange sounds that could be EVP (electronic voice phenomena). They learn that seven people survived the crash, including Jerry's friend, the pilot, Chuck Lambert. When they analyze the footage further, they hear an unearthly voice saying "no survivors," and they discuss various stories of spirits and omens on ships and planes. They go to visit one of the survivors of the crash, a man named Max who has checked himself into a psychiatric hospital, and he admits that he saw the black-eyed man open the emergency door, even though such a thing should be physically impossible. They next visit the widow of man who opened the door, and she says that her husband had had a fear of flying, but can think of nothing else strange to tell them.
Using fake Homeland Security badges (and newly-purchased suits), Sam and Dean gain access to the wreckage of the plane and find a strange substance on the door handle of the emergency exit, which turns out to be sulfur, leading them to realize that they are dealing with demonic possession. At the same time, the pilot, Chuck Lambert, flies a twin-engine plane with a friend to regain his confidence, but he is possessed by the same energy and deliberately crashes the plane forty minutes into the flight. Jerry calls Sam and Dean and tells them of Chuck's death, and they realize that the forty-minute mark is Biblically symbolic. They remember the voice saying "no survivors" and realize that the demon is going after those who survived the first crash. Dean calls them all and confirms that they are not flying any time soon, except for one woman, Amanda, a flight attendant. The brothers speed to the airport and make a phony phone call to delay her next trip, but it fails and she gets onboard. Knowing the demon will go after her and presumably kill all of the other passengers in the process, Sam says that they have to get on the plane as well and exorcise the demon, but Dean is hesitant and finally reveals his fear of flying. He gives in, however, realizing they have no other choice.
Once on the plane, Dean attempts to keep himself calm ("Are you humming Metallica?") as they speculate as to which person the demon is possessing. They guess that it is Amanda herself, but when Dean tests this theory by saying the Latin word "Christo" in her presence, he realizes it is not her. He uses his homemade EMF meter to check the other passengers, and soon discovers that it is the co-pilot who is possessed. They talk to Amanda and explain the connection with her other crashed flight, and convince her to help them by summoning the co-pilot to the back of the plane. Once he is there, the boys overtake him with holy water and Sam attempts an exorcism from John's journal, but is briefly distracted when the demon taunts him about Jess' death. They finally manage to extract the demon from the man's body, but it quickly goes into the vent and overtakes the plane. As it speeds towards the crowd, the passengers--and Dean--panic, but Sam manages to finish the incantation and sends the demon back to Hell, causing the plane to right itself in the air. Once on the ground, the police take statements from the passengers, and Sam and Dean leave quietly. Sam asks how the demon could have known about Jess' death, but Dean just tells him that they can read minds and often lie. Jerry thanks the boys for their help, and Dean asks how he got his new cell phone number. Jerry says that John provided it, and the brothers call their father yet again and are shocked to hear a new outgoing message, confirming for the first time that he is still alive and has possibly disappeared on purpose.