The F+B Ambulance Company is locked in an intense battle with the Unity Ambulance Company to win a city contract for providing ambulance service to a territory within Los Angeles. Their star driver is "Mother" Tucker [Bill Cosby], a talented antihero who drinks alcohol on duty, harasses nuns, and behaves brazenly toward practically everybody he meets, including his partner Leroy [Bruce Davison]. Indeed, the entire company is a band of misfits, including the hypersexual Murdoch, John Murdoch [Larry Hagman], his partner Walker [Michael McManus], putative medical student Bliss [Allan Warnick], and brash Texan "Rodeo" Moxey [Dick Butkus]. The dispatcher and switchboard operator is Jennifer, Raquel Welch, whom the drivers nickname "Jugs" for her ample bosom. Harry "Doughnut" Fishbine [Allen Garfield] runs the company, using occasionally underhanded means (such as kickbacks) to maintain an income stream. Naomi Fishbine [Valerie Curtin], his wife, is also involved in the unfolding business landscape.
When Walker is injured after falling through a staircase on a call, Harry Fishbine hires Tony Malatesta [Harvey Keitel], a disgraced sheriff's detective and former Vietnam War ambulance driver. Upon learning that Tony has been suspended from the Sheriff's Department due to allegations that he sold cocaine to children, Mother renames him Speed and he is quickly paired with Murdoch. Speed's partnership with Murdoch is rocky, especially when Speed must intervene to stop Murdoch from raping an unconscious female college student who has overdosed on Seconal. On a false emergency call, Leroy is shot and killed by a junkie (Addict [Toni Basil]) demanding drugs. When Mother pulls a gun on the junkie, the junkie commits suicide. Later that night, a drunken Mother assaults Murdoch for saying Leroy's death "doesn't count"; Murdoch was speaking about the "dead body" pool, but Mother takes it as a personal insult. Harry then pairs Speed with Mother to alleviate his driver shortage.
Meanwhile, Jugs—Jennifer [Raquel Welch]—obtains her Emergency Medical Technician (EMT) certification and forces her way onto F+B's active roster with threats of sexual discrimination lawsuits. When Speed fakes an injury to prevent Jugs' arrest for misuse of an ambulance, the two fall in love. Though Jugs proves a capable EMT, she loses her nerve after a pregnant woman under her care bleeds to death in Mother's ambulance. Jugs withdraws, then regains confidence under Mother's encouragement and returns to work.
At a City Hall meeting, City Councilman Warren informs the owners of both Unity and F+B that the contract will not be awarded to either; it will instead go to a larger company. To save their business, Unity's owner Charles Taylor [Bill Henderson] proposes a merger. The councilman approves, but Fishbine resists. The evening takes a violent turn when Murdoch, intoxicated and armed, breaks into the F+B garage with Walker and holds Mrs. Fishbine [Valerie Curtin] hostage. All of Unity's and F+B's ambulances descend on the garage; Murdoch fires at Speed, who has moved to defend the operation. Speed is wounded in the shoulder, and the confrontation ends when a deputy sheriff shoots and kills Murdoch, ending the immediate crisis.
In the aftermath, F+B merges with Unity, forming Fishbine + Unity (F+U) Ambulance Company, headquartered in the old F+B garage. Speed, who has been cleared of charges, is reinstated to the Sheriff's Department, though he remains romantically involved with Jugs. Jugs is initially relegated again to switchboard duty, until Mother insists she becomes his new partner. The film closes with the two driving off together, and Mother once again teasing the nuns as they roll away.
