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The onscreen screenwriting credit reads: "Screenplay by Fay and Michael Kanin." The opening and closing cast credits vary slightly in order. A written foreword reads: "Manhattan Island... A body of land consisting of four million square miles-completely surrounded by women." Throughout the film, Ann Sheridan provides voice-over narration as her character, "Amanda Penrose." The Opposite Sex was based on the 1936 play by Clare Boothe Luce (credited onscreen as Clare Boothe) entitled The Women. A previous adaptation of the play, also called The Women, had been produced by M-G-M in 1939, directed by George Cukor and starring Norma Shearer, Joan Crawford and Rosalind Russell (see AFI Catalog of Feature Films, 1931-40). The screenplay for that version was written by Anita Loos and Jane Murfin and, like the play, contained no onscreen male characters. In a February 19, 1956 Los Angeles Times article, the Kanins stated that the studio included men in The Opposite Sex because "you can't play a love scene alone." Although that article also noted that there would be no big production numbers in the picture, several were included in the final film.
Modern sources state that M-G-M originally considered Grace Kelly for the role of "Kay Ashley Hilliard." In May 1955, Daily Variety announced that M-G-M was preparing The Opposite Sex for Esther Williams. By August 1955, according to an Hollywood Reporter news item, the studio planned to star Doris Day and Howard Keel in the film, but later cast Eleanor Parker in the lead role. As noted in a November 29, 1955 Hollywood Reporter item, Parker refused the role, citing her desire to rest after a strenuous two-year schedule, and was subsequently placed under suspension by M-G-M. A December 1955 "Rambling Reporter" piece in Hollywood Reporter stated that Peter Graves was considered for the role of "Buck Winston," and as of February 19, 1956, a Los Angeles Times article about the film included Vivienne Segal in the cast as "Countess." In March 1956, however, Hollywood Reporter noted that Segal withdrew from the production because "the broadness of the script characterization was too pronounced for her," and the role was taken over by Agnes Moorehead. Although a January 13, 1956 Hollywood Reporter news item adds Arthur O'Connell to the cast, he did not appear in the final film. Another Hollywood Reporter news item states that dancer Roberta Lane was cast, but her appearance in the film has not been confirmed.
Dolores Gray sang the title song over the opening credits. According to a 26 April Hollywood Reporter item, the titles were to run over five pantomime vignettes written by Sammy Cahn, but no vignettes were seen in the viewed print. Contemporary sources note that some scenes were filmed on location in New York City. An article in the October 1956 issue of Cosmopolitan claimed that Joan Collins contracted a severe allergy to bath bubbles, making her two bath scenes painful, and that during the scene in which Kay slaps "Crystal Allen," June Allyson's punch knocked Collins unconscious. The article added that Allyson was paid $3,000 per day for her role in the film.
Upon the release of The Opposite Sex, many critics compared the picture unfavorably to the earlier film version, stating that the biting humor of Luce's original play had been lost. In addition, the Motion Picture Daily reviewer expressed disappointment that celebrated entertainers Gray and Ann Miller were not given the opportunity to sing or dance in the film. The film marked Allyson's last role at M-G-M, where she had been a contract player since 1942.