In Los Angeles, California, aspiring novelist Larry Donner suffers from writer’s block as he attempts to begin a new book. He turns on the television and sees his ex-wife, Margaret, discussing her best-selling novel, Hot Fire, on a daytime talk show. Larry yells at the television, accusing Margaret of stealing his book. Elsewhere, the middle-aged, downtrodden Owen Lift tends to his verbally abusive “Momma.” When she demands a soda, Owen decides to poison her by pouring lye into the drink. However, just as she is about to take a sip, he has second thoughts and bats the cup out of her hand. Later, he attends a community college writing class, taught by Larry Donner. After class, Owen follows Larry to a Laundromat and demands to know what the teacher thought of his story, “Murder at My Friend Harry’s.” Larry tells Owen that his characters lacked motivation and drives away. At home, Larry calls a woman named Beth and leaves her a message, apologizing for missing their date. He returns to the blank page in his typewriter. Still uninspired, he types several variations on the opening line, “The night was hot,” but gets no further. The next day, he finds Beth, an anthropology teacher at the community college, on campus. He apologizes again for missing their date, and she agrees to give him another chance. Several of Larry’s students, including Owen, eavesdrop as Larry complains about his writer’s block and his lack of passion. Beth argues that he is passionate about one thing: his ex-wife, Margaret. As Beth walks away, Larry shouts that he hates Margaret and wishes she were dead. Owen hounds Larry for a meeting to discuss his story. When they finally get together, Larry explains that a good murder mystery must eliminate the killer’s motive and establish a plausible alibi. He tells Owen to go see an Alfred Hitchcock film for inspiration. Later, Owen watches Hitchcock’s Strangers on a Train, in which the two leading characters agree to “swap murders,” eliminating each other’s motives. Having overheard Larry’s tirade against his ex-wife, Owen assumes his teacher wants to swap murders with him. He flies to Hawaii, where Margaret Donner lives. Meanwhile, Larry’s agent, who recently signed Margaret as a new client, drops Larry, who goes to the beach to drown his sorrows. Meanwhile, in Hawaii, Owen follows Margaret Donner onto a ferryboat. As Margaret leans out over the railing, Owen creeps up behind her. The next morning, Larry is awakened by a call from Owen, who announces that he fulfilled his side of the bargain by murdering Margaret. Dumbfounded, Larry insists there was no bargain. He hangs up and runs to his neighbor Lester’s apartment. He rambles incoherently about needing an alibi, and asks to borrow Lester’s car. Driving to Beth’s house, Larry hears a radio news report confirming Margaret’s disappearance and continues to panic. He explains the ordeal to Beth, who is disturbed by the news, and sends him away. That night, when Owen returns from Hawaii, Larry picks him up at a bus station and demands that he confess to the murder. He attempts to scare Owen into submission by speeding, but loses control of the car and runs off the road. They retreat to Owen’s house, where Larry meets the cold-hearted “Momma,” and begins to understand Owen’s alienation. Owen begs Larry to suffocate Momma with a pillow and leaves the house to go bowling. In Owen’s absence, Larry searches for evidence he can use to incriminate Owen. However, he discovers that Owen purchased a ticket to Hawaii under Larry’s name. Larry is about to leave the house when police arrive to question Owen, who returns home just in time to invite them inside. Owen is disappointed to find Momma still alive and Larry hiding in the pantry. He toys with the idea of turning Larry over to the cops, but does not go through with it. Later, he reprimands Larry for his inaction. Owen sets up a trap for his mother to fall down a flight of stairs, but Larry falls down the stairs instead. Hours later, he regains consciousness and finds Owen trying to kill Momma by blasting a loud horn in her ear. Momma awakens and sees a television news report identifying Larry as the prime suspect in Margaret’s disappearance. She threatens to call police and Larry flees. He boards a train to Mexico. Owen and Momma follow, and the three ride in a train car together. Larry tells Owen he has resolved himself to this turn of events. He believes he has a great ending to a new story, based on his and Owen’s ordeal, but he wonders how to begin, and asks which opening line is better: “The night was humid,” or “The night was moist.” Momma states matter-of-factly that the line should be, “The night was sultry.” Finally driven to kill her, Larry chases Momma through the train. When she reaches the caboose, she loses her balance and falls out. Larry tries to rescue her. Having had a change of heart, Owen arrives and helps Larry pull Momma to safety. Momma praises Owen but kicks Larry off the train. He recuperates from the fall in a hospital, where he turns on the television and sees Margaret being interviewed. She tells a news reporter that she fell overboard when reaching for her diamond earring, and was rescued by a Polynesian fisherman she now plans to marry. She has already sold film rights to her story for $1.5 million. That night, Larry has nightmares about killing Margaret. He wakes up inspired and begins to write. A year later, Owen reunites with Larry at his apartment. Larry has just finished the manuscript for his new novel, Throw Momma from the Train, based on his experiences with Owen and Momma. Owen informs Larry that he recently sold a book about the same thing, titled, Momma and Owen and Owen’s Friend Larry. Believing that his book idea has once again been stolen by another writer, Larry strangles Owen. However, he stops short when Owen produces a copy of the book, which is a children’s book with pop-up illustrations. The final chapter shows Larry, Owen, and Beth taking a trip to Hawaii together. Sometime later, Larry’s book has been published. Beth praises it as she, Larry, and Owen relax on a tropical beach.