|A man, obviously terrified of flying, is splashing water on his face when a black smoke-like substance comes from the ventilation shaft and enters his body, leaving him with black eyes. He gets on his plane, worrying the stewardess when she sees him. 40 minutes into the flight he gets up and calmly walks to the rear of the plane and opens the door - causing instant depressurization. The plane hurtles towards the ground.
5:45 the next morning and Dean is woken up by Sam. They discuss the nightmares that Sam is still having until Dean receives a call on his cellphone. Jerry Panowski is someone that Dean and John helped out with a Poltergeist problem a few years earlier. He has another problem that he thinks is right down their alley. They head over to his office where he plays them the cockpit voice recording from flight 2485 that crashed. He reveals that they have no idea what could have caused the crash, but he thinks Dean and Sam might be able to help. They listen to the recording and hear a voice saying "No Survivours" which confuses them as there were seven people who survived the crash.
One of the survivours checked himself into a pyschiatric home shortly after the crash. When Dean and Sam talk to him (posing as Homeland Security) hesays he thinks he saw a man opening the door, which cant possibly be true, hence the reason he checked himself in. Sam and Dean go off to talk to this man's wife who insists that there was nothing unusual about her husband. They had thought he must be something other than human to have been able to open the door, but it seems not. The next thing for them to do is check out the remains of the airplane.
Thanks to their Homeland Security ID, they manage to get in and discover sulphur on the emergency door handle - something which could only have come from a demon. When the real Homeland Security guys arrive, Dean and Sam run.
Meanwhile, Chuck Lambert, the pilot from flight 2485 is about to fly a small plane for the first time since the crash. As he is preparing himself, the same black smoke that entered the first man does the same to him. 40 minutes into his flight, he purposely crashes the plane he is flying.
Jerry tells Dean and Sam about the second crash and they realise that there must be some kind of demonic possession happening and that the demon wants to kill everyone that was on the original flight. Panicked, they call the rest of the survivours, but of them all, only the stewardess, Amanda, is preparing to fly again. They use all their tricks to try and stop her getting on the plane, but it doesn't work, so they do the next best thing - they get on the flight too, despite Dean's fear of flying.
They test several people to see who the demon is possessing and it is eventually revealed to be the co-pilot. With some help from Amanda, they begin an exorcism. The demon leaves the human body, but becomes more powerful and causes the pilot to loose control of the plane. Ignoring the panic and chaos that surround him, Sam manages to complete the exorcism, destroying the demon and allowing the pilot to regain control of the plane.
They head back to say goodbye to Jerry and ask how he knew to contact them. He says that when he phoned John's cellphone, there was a message saying to call Dean in case of an emergency.