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Gerald Green's novel, although a work of fiction, was based on the life of his father, a Brooklyn physician. In a Los Angeles Times article, director Daniel Mann noted that while the novel covers the entire life of the fictional character "Dr. Sam Abelman," the film only focuses on his last days. Mann hoped that the film would "illuminate...the meaning of the book." A 1956 Los Angeles Examiner news item reported that Columbia studio head Harry Cohn paid $250,000 for the film rights to Green's manuscript, and that Marlon Brando was initially offered the lead role. 1957 Los Angeles Examiner news items reported that Cohn was considering producing a stage version of the novel starring Paul Muni before making the film, and that Vera Caspary had written a screenplay for Columbia based on the novel. The play was never produced, however, and Caspary's contribution to the final film has not been determined.
Hollywood Reporter news items reveal the following information about the production: Glenn Ford was initially cast as "Woodrow Wilson Thrasher" but withdrew from the project. Jack Lemmon was then assigned to the role, but walked off the project, claiming he was exhausted from a hectic schedule. A 1958 news item noted that Peter Ustinov was originally to play Dr. Sam Abelman. Other 1958 news items add that Melvyn Douglas, Sam Levene and Bob Morse were also considered for parts in the picture. Although various news items place Philip Media, Robin Starling, Tom Cleaver and Michael Day in the cast, their appearance in the released film has not been confirmed.
The film was partially shot on location in Brooklyn, NY, according to Hollywood Reporter news items. Various reviews praised the film for its ethical content and fine performances. The National Catholic Legion of Decency gave the film its highest rating, and added the following notation: "The self-sacrifice and dedication to humanity which characterized the life of the protagonist are intellectually rewarding as well as heartwarming. The film can serve as an inspiration to people of all races and creeds." The film, unlike the novel, does not overtly state that Dr. Sam Abelman and his family are Jewish; however, the characters do state that they are Russian immigrants.
The picture marked Paul Muni's first American film since 1946, and his final screen performance before his death in 1967. The Last Angry Man also marked the screen debuts of Billy Dee Williams, Godfrey Cambridge and Claudia McNeil. The film was nominated for Academy Awards for Best Actor (Muni) and Best Art Direction (black & white). On April 24, 1974, the ABC network aired a television version of the novel, also titled The Last Angry Man, written by Green, and starring Pat Hingle.