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Ethel "Pug" Wells, who made a very brief appearance in the film, was an actual American Airlines stewardess. According to M-G-M press releases, Wells, who was originally from Clarkson, MI, made an eighty-city tour to publicize the picture. According to reviews and M-G-M publicity, some of the incidents in the film were based on her experiences. A Los Angeles Times article on February 14, 1951 related that on one of her flights to Los Angeles, Wells had so intrigued director William Wellman with stories of her experiences that by the end of the flight Wellman determined to make a movie about her. No source mentions any specific involvement of Wellman in Three Guys Named Mike, however.
An M-G-M press release from May 1950 stated that June Allyson was initially set to star in the picture. Allyson became pregnant, however, and was unable to appear in the film. A May 2, 1950 Hollywood Reporter news item stated that Robert Walker had been cast opposite Allyson and Van Johnson. Several of the film's early scenes show the type of training that stewardesses receive at the American Airlines school. According to a February 12, 1951 Hollywood Reporter news item, producer Armand Deutsch planned a sequel to the film, but it was never made.