A fleet of helicopters sprays for medflies and reveals all the characters along the path of their flight. Dr. Ralph Wyman (Matthew Modine) and his wife, Marian (Julianne Moore), meet another couple, Stuart (Fred Ward) and Claire Kane (Anne Archer) – an out-of-work salesman and a party clown respectively – at Zoe Trainer’s (Lori Singer) cello concert and make a spontaneous Sunday dinner date.
Marian’s sister, Sherri (Madeleine Stowe), is married to philandering cop Gene (Tim Robbins), who invents unbelievable stories to hide his affair with Betty Weathers (Frances McDormand). Betty is in the process of divorcing one of the helicopter pilots, Stormy (Peter Gallagher). Waitress Doreen Piggot (Lily Tomlin) is married to an alcoholic limo driver, Earl (Tom Waits).
Television commentator Howard Finnigan (Bruce Davison) lives with his wife, Anne (Andie MacDowell), and their young son, Casey (Zane Cassidy), next door to Zoe and her mother, cabaret singer Tess (Annie Ross). Their pool cleaner is Jerry Kaiser (Chris Penn), whose wife, Lois (Jennifer Jason Leigh), works from home as a phone sex operator, tending to the children while she talks off strange men. Jerry and Lois are friends with Doreen’s daughter, Honey (Lili Taylor), and her husband, Bill (Robert Downey Jr.), who works as a makeup artist.
The day before the eighth birthday of Casey, Doreen hits him with her car as he is running to school. Casey appears fine and refuses Doreen’s offer of a ride home, as she is a stranger. His mother Anne comes home from ordering his birthday cake to find him slumped lethargically on the couch. His father Howard convinces her to take Casey to the hospital, where he remains unconscious. The baker, Andy Bitkower (Lyle Lovett), calls the next day to inform Ann that the cake is ready, but Howard, wanting to keep the line free, briskly ends the conversation. The baker immediately calls back, incensed at being hung up on. While the Finnigans maintain their vigil, Bitkower continues to call and harass the couple. Howard’s estranged father Paul (Jack Lemmon) turns up at the hospital and recalls that Casey’s hospitalization reminds him of the day that Howard was in a car accident as a boy. When Howard’s mother went to her sister’s house, she found her undressed in the presence of her husband, whom she was attempting to seduce. That led to the estrangement between father and son.
Stuart and his two friends, Gordon (Buck Henry) and Vern (Huey Lewis), harass Doreen at the diner before they head out on their three-day fishing trip. On the first day, they find a young woman’s body, submerged near some rocks. After some debate, they decide to tie her to the rocks, continue fishing, and report the body when they are done. When he comes home, Stuart eventually admits to Claire what they had done, and she is disgusted that they could fish for days with the woman’s body nearby. The body is identified as a 23-year-old woman who was raped and murdered, and Claire visits the funeral home out of a sense of guilt.
Stormy visits Betty’s house while she is away with their son Chad (Jarrett Lennon), ostensibly to pick up his mother’s clock, but instead spends the day destroying her belongings. Bill and Honey entertain themselves in the apartment that they are watching while its owners are on vacation by taking some pictures of Honey in which Bill has made her up to look as if she has been brutally beaten. Gene abandons the family dog on a strange street because he cannot endure its barking, but after several days of his distraught children’s inquiries, he returns to the neighbourhood and retrieves the dog, who has been picked up by Vern’s family. The Wymans get into a massive argument just before their dinner party with the Kanes. Marian admits to an affair. Both couples alleviate their stress by drinking heavily, and the party lasts all night long.
One day, Casey’s eyes begin to flutter. Ann’s excitement grows, but just as he appears to be fully waking, he suddenly dies. Seeing that and being overwhelmed, Howard’s father, Paul, leaves the hospital while the distraught couple returns home and informs Zoe of Casey’s death. The next day, they go to the bakery to shame Bitkower over his abuse of them. When he learns why they never picked up the cake, he asks them to stay and gives them baked goods. Zoe, worn to the breaking point by her mother’s alcoholism and her isolation, commits suicide by starting a car engine inside her garage; she plays the cello as she asphyxiates. Later that day, her mother discovers Zoe’s death and is bewildered.
When Honey picks up the pictures from the developer, they are mixed up with Gordon’s. He is horrified to see the pictures of Honey, who is apparently beaten so badly, and she is horrified by the pictures Gordon took of the submerged body on his fishing trip. They walk away from each other, memorizing each other’s license plates. Honey and Bill are on their way to a picnic with Jerry and Lois. In the park, Jerry and Bill meet two young women they encountered earlier, and Bill quickly makes an excuse to divvy up into couples. As he and one of the girls walk away from Jerry and the other girl, they hear her scream. They turn around to see Jerry hitting her in the head repeatedly with his beer can, killing her, just before a major earthquake strikes. In the aftermath, Jerry’s murder of the girl could be attributed to a falling rock during the earthquake.