Mac Taylor is on a plane to Washington D.C. from New York. The flight is shaken by turbulence and the man sitting next to Mac, an inventor named Ed Riley, becomes anxious. Mac tries to calm him down as the plane stabilizes and the fasten seatbelts light turns off.
Mac notices a flight attendant close the front curtains and then the rear curtains. Mac walks to the back and sees a group of attendants whispering. He identifies himself and the staff shows him a dead man in the bathroom stall. One of the attendants, Susan, says that she discovered him after seeing blood coming from under the door.
Mac checks the body and finds that he was killed by a stab wound to his neck. The man has a Federal Air Marshal badge and an empty gun holster. Mac asks one of the attendants, Nina, to bring him a first aid kid and the passenger manifest. He instructs the pilot to turn around and head back to New York with the excuse that someone onboard needs medical attention. He tells the crew to turn on the seat belt sign and act like normal.
Mac returns to his seat and tells Ed that someone was murdered on board. Ed freaks out and Mac tells him that he is the only person he can trust because he was beside him the whole time.
Mac takes Ed to the bathroom and asks him to watch his back while he investigates the crime scene. Nina arrives with the first aid kit and the passenger list. Mac puts on a pair of gloves and searches the body. He notices that the man is missing his wallet and then asks Nina to transmit the Air Marshal badge number to the authorities to figure out who the victim is.
Nina tells Mac that he was sitting in row 6. Mac goes to the row and sits down to look for the victim's wallet. He looks around and sees an empty cup in row 11 but no one sitting there. He checks the list and sees that a man named James Tartar was assigned that seat. The attendant tells Mac that he was agitated and asked for a glass of water. They look down the aisle and the attendant points the man out, sitting in a different seat. Mac walks by and notices a red stain on the cuff of his shirt. Mac returns to the attendant station and Nina tells him that the badge belongs to a Roger Stockwell and his description does not match the victim in the bathroom. Nina brings Mac some lipstick and he applies it to the victim's fingers. He then places the prints on a piece of paper. Nina brings Mac a satellite phone she got from the pilot and he sends photos of the prints to the crime lab.
Mac then calls Detective Stella Bonasera in New York. He instructs her to secure a hangar at the airport because he is bringing in a crime scene.
The lab identifies the prints as belonging to a Anton Greenway, a escapee who was convicted for drugs.
The team learns that Stockwell never checked into work that day and that he was staying at a New York Hotel.
Detectives Danny Messer and Don Flack go to the hotel to check it out. They enter the room and find Stockwell's body lying on the floor with bruises on his arms and a gunshot wound to his head. They investigate further and find animal hair, duct tape, a .50 Caliber Desert Eagle and a teddy bear that they believed was used as a improvised silencer.
The plane lands in New York and is brought into a hangar where the CSI team are waiting. The police enter the plane and Mac tells everyone that there was a murder on the plane and that the passengers will be questioned. Mac grabs James Turner and asks the police to search him first.
After disembarking the plane, Mac is told that the Department of Homeland Security will allow the police to detain the passengers for only 24 hours.
The team discovers that James paid in cash for a one way ticket to Washington DC. Mac brings him in and asks what his plans are. James admits that he was trying to hide his travels because he has a second family that his first wife does not know about. Mac orders him to remove his clothes so the team can examine his stain.
The team inve