By most accounts Dr. Sam Abelman is a failure in life, an irascible old general practitioner who lives in the same grimy Brooklyn neighborhood he has always lived in. He is truculent and tactless, an easy mark for the young specialists who steal his patients. One night a bunch of hoodlums drop a battered young woman on his doorstep. Abelman's nephew, a reporter, publishes a news item about the incident, "Doctor Saves Raped Girl."

Meanwhile, Woody Thrasher, vice president of an advertising agency, is looking for a new type of television show to sell to one of his clients. He comes up with Americans USA, a candid look at "ordinary" Americans who are just doing their jobs, but in an extraordinary way. He decides that Sam Abelman would be the ideal first subject.

Thrasher, a young, high-powered executive, meets Abelman, the last angry man, who summarizes his view on life by saying, "The bastards just won't let you live." The doctor's practice is declining, he can't afford to retire or move away, and the local people certainly don't seem to love him. They don't show gratitude for his services. They don't pay their bills. Many of them consider him a racist, and incompetent to boot. Abelman is clearly not a good candidate for "doctor of the year."

Yet, Thrasher soon finds himself intrigued. Abelman spends hours working in his miniature vegetable garden and reading Henry David Thoreau. He is a brilliant diagnostician, a devoted husband, and an endless campaigner against the "galoots" who think the world owes them a living. Abelman takes aim at "galoots" wherever he finds them, and he finds them everywhere.

The novel interweaves these two men's developing relationship, as Abelman agrees to do the show and Thrasher works to sell it to his bosses, with incidents from Abelman's earlier life. When it turns out that Americans USA will award its subjects their "heart's desire" (in Sam Abelman's case a new house), the doctor declines to go on, refusing to accept "charity" and claiming that Thrasher "tried to crap me up." In the end he agrees to do the show, but suffers a massive heart attack and dies.