Janice Rule was born in Norwood, Ohio, to parents of Irish origin. Her father was a dealer in industrial diamonds. She began dancing at the Chez Paree nightclub at fifteen, which paid for ballet lessons, and was a dancer in the 1949 Broadway production of Miss Liberty.Rule also studied acting at the Chicago Professional School. She was pictured on the cover of Life magazine of January 8, 1951, as being someone to watch in the entertainment industry. Given a contract by Warner Bros., her first credited screen role was as Virginia in Goodbye My Fancy (1951), which featured Joan Crawford in the lead. The established star though, belittled the younger woman, making her work on the film difficult, although it should be noted that Joan Crawford years later wrote a letter of apology to Ms. Rule for treating her badly on this film. and Rule's Warner contract was allowed to lapse after only two films.She was troubled by the attitude toward women's beauty at the studios in the early 1950s: "Because I was afraid of being robbed of my individuality, I fought with the makeup people, the hairdressers, and I didn't understand problems of the publicity department," she was reported as saying in 1957. Rule was in the original 1953 Broadway cast of William Inge's Picnic (in the role of Madge Owens, the innocent beauty, played by Kim Novak in the film version) whose company also included Paul Newman who was making his debut on Broadway. This commitment led her to turn down the role ultimately played by Eva Marie Saint in On the Waterfront (1954). "I knew I couldn't shoot in a movie all day and work on a stage at night and do my best in both," she was quoted as saying by Hedda Hopper of the Los Angeles Times in 1966. Among her other Broadway shows were The Flowering Peach, The Happiest Girl in the World and Michael V. Gazzo's Night Circus, a 1958 production which lasted for only a week, but introduced Rule to Ben Gazzara, who became her third husband
Her other films in the 1950s included A Woman's Devotion (1956), the Western Gun for a Coward (1957) and Bell, Book and Candle (1958), in which she played the fiancée who loses publisher 'Shep' Henderson (James Stewart) to the spell-casting witch Gillian Holroyd (Kim Novak). On television she appeared in the Checkmate episode "The Mask of Vengeance" (1960), where she played Elena Nardos, the roommate of Cloris Leachman's character, Marilyn Parker. She was also in The Twilight Zone episode "Nightmare as a Child." She appeared as different characters in three episodes of Route 66. She acted as both Barbara Webb and Barbara Wells opposite David Janssen in two episodes of The Fugitive entitled "Wife Killer" and "The Walls of Night". She also had a major role as Nancy Reade in "Three Bells to Perdido", the first episode of Have Gun – Will Travel. Among her later film roles were Emily Stewart in The Chase (1966), Burt Lancaster's bitter ex-lover in The Swimmer (1968), Willie in Robert Altman's 3 Women (1977), journalist Kate Newman in Costa Gavras' political thriller Missing (1982), and Kevin Costner's mother in the bicycle racing film American Flyers (1985).
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