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A University of Texas professor of philosophy and capital punishment abolitionist, David Gale, is on Death Row convicted of the rape and murder of his best friend, Constance Harraway, who was the leader of the local branch of Death Watch, an organization campaigning against the death penalty. Days before his execution, skeptical journalist Bitsey Bloom is sent by the weekly news magazine where she works to conduct David Gale's final interview. She is accompanied by intern reporter, Zack Stemmons.

Gale's lawyer is Braxton Belyeu, an ageing eccentric with a long ponytail. We learn that Gale asked specifically for Bloom, and will talk only to her. They are to have two hours on each of three consecutive days, after which Gale will be executed at 6 o'clock in the evening of the fourth day. Belyeu and Stemmons leave the prison and Gale starts to tell Bloom his story, which we see in a series of flashbacks.

Gale's marriage was in difficulties, and relations with his wife Sharon strained, but he was devoted to his small son Jamie. We see Gale lecturing on philosophy to a large class of students. Then a couple of minutes before the end of the lecture period a beautiful female student named Berlin arrives noisily and Gale pauses while she takes her seat. As the students leave after dismissal, Berlin apologizes for being late and tells Gale she'll do "anything" for a better term mark. He tells her quietly but firmly that the way to get a better mark is to study. However, not long after that Gale finds himself one evening at a party with faculty and students, and Berlin catches him alone in a luxurious bathroom. Locking the door, she tells him she isn't his student any more (since she's been expelled from school), and that she wants sex with him anyway.

Gale gives in to temptation but soon finds himself accused of rape. His world falls apart: he loses his university post; his wife leaves him, taking their son, selling their house and moving to Spain; even the national leader of Death Watch (by phone) wants local organizer Constance Harraway to have no more to do with him. We see Gale sitting distraught on the step of the path to his house front door, clutching his little boy's favorite soft toy to him, as his wife and son are driven away in a taxi; we see him in a conversation with a university dean who explains there is no way he can give Gale a job because of his reputation; and we see him in an interview attempting to get a job in business and hopelessly lost when asked to give three reasons why they should hire him. Gale, now jobless and homeless, turns heavily to drink; we see him in a bar, then staggering along a crowded sidewalk at night shouting about Socrates, Plato, and Aristotle to passers-by; and at last he winds up on the porch of his only remaining friend in the world, Constance Harraway. He now learns, as a result of an emergency when she has to go to hospital, that she is dying of leukemia. He has to sleep off his drunken stupor on a seat in the hospital corridor. After she is home again, Constance is talking to David one evening about her one regret in life, that she didn't have more sex. He offers and, having assured her it isn't out of pity, she accepts. He leaves in the morning but she is subsequently found dead --- naked, handcuffed behind her back, with her mouth taped over with gaffer tape, and suffocated by a plastic bag that is over her head and taped round the neck. An autopsy reveals that she had swallowed the handcuff key. David Gale's semen is also found inside her. A tripod --- on which no fingerprints were found --- is present, though no camera or videotape is found.

Bloom and Stemmons visit Harraway's former house, which has been turned into a sort of museum with a "tour" of the crime scene by the current tenant Nico, a plump young woman with a goth appearance.

After the prison visit one afternoon, Bloom and Stemmons collect half a million dollars in cash in a shiny brief case. The money is the "fee" paid by their magazine to Gale for the exclusive interview. They then return to their motel to find her door blocked open with a roll of gaffer tape, and a videotape cassette suspended by a string from the ceiling of her room, labelled with her name. They borrow a video player from the motel manager and are profoundly shocked to find that the tape has the last few minutes of Constance Harraway's life, of her naked, cuffed and suffocating on her kitchen floor.

From time to time while driving between the motel and the prison, Bloom and Stemmons have noticed a lean figure of a man in a stetson hat, apparently following or watching them. They discover who this man is: Dusty Wright, a secretive loner but a follower and admirer of Constance Harraway. Bloom delivers the attaché case full of cash to the lawyer Belyeu's office, and spies Wright entering just as she is leaving.

Assuming that Gale is telling the truth when protesting his innocence of the rape and murder, there is speculation as to who did the murder and apparently framed him. Candidates include some mysterious group trying to discredit the abolitionist cause.

However, after the third and last interview with David Gale at the prison, at the end of which he takes his leave saying he'll be dead by the end of the next day, Bloom and Stemmons return to the "museum" with handcuffs and gaffer tape, and Bloom re-enacts the death scene using the handcuffs, the tape, and a plastic bag. She tells Stemmons to wait three minutes before freeing her, but he and Nico can't bear to watch her struggle and he has to tear the bag open, afraid Bloom is actually suffocating herself. The outcome of the experiment, given what they know about her dedication to her cause and the fact she had only a short time to live anyway, is their conclusion that there was no murder: Constance Harraway committed suicide, deliberately intending to make it look like murder of her by Gale, because of his ruined reputation after the affair with the girl Berlin. She had willingly made love to Gale in the hours before killing herself, setting him up for the additional charge of rape.

They then realize that, having been given the brief tape, there must exist a full recording of the suicide, and that Harraway's purpose was almost certainly to have Gale exculpated at the last possible moment by production of the recording that must prove she committed suicide unaided. However, whoever was supposed to produce the tape has not done so. They realize that this must be Dusty Wright, and that he has an agenda of his own. Jealous of Gale's relationship with Harraway, he has not produced the full tape recording because if saving Gale at the last minute would make news as a momentous case against the death penalty, allowing Gale to die before revealing that he was innocent would make the case even more strongly.

At the last minute, they go to Wright's home and Bloom searches frantically for the full tape, while Stemmons keeps watch for any sign of Wright. She finds the tape, having to play it through and watch it to see that it is what she needs. After Hallaway dies, Dusty Wright appears in front of the camera, showing that he helped the woman in her plot against Gale. There is then a frantic journey to the prison, to try to get there and have the tape seen before Gale is executed. The car breaks down some distance away and the final scenes are of Bloom frantically running along the street trying to reach the prison before the deadline. We see the ritual leading to the execution being followed. There are calls from the state Governor's office giving final go-ahead. Outside the prison, we see a large group of demonstrators from Death Watch, part of a large crowd including police officers.

Bloom reaches the crowd and makes her way through the throng only to hear an announcement from a prison official that Gale had died some minutes earlier.

Back at her desk at work, Bitsy Bloom receives a Fedex package containing the favorite soft toy of Gale's young son Jamie, left behind with the father when the son went abroad. Inside it is a video cassette with an additional segment at the end revealing that Gale was in the kitchen when Hallaway committed suicide. In this way Gale wanted to relieve the journalist from the guilt of not saving him.

Meanwhile Dusty Wright, very smartly dressed now, travels to Europe and delivers the silver attaché case full of cash as well as a postcard proving his innocence in his earlier alleged rape to the new residence of Sharon Gale. He rings the apartment doorbell and disappears, leaving the case anonymously at front of the door.