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The working title of this film was Miami. Although a December 23, 1940 Hollywood Reporter news item stated that Twentieth Century-Fox had purchased an "original" entitled Miami by Stephen Powys, the film was based on Powys' play Three Blind Mice. Although the end credits list Don Ameche's character as "Phil O'Neil," in the film he is called "Phil McNeil." According to an December 11, 1940 script conference with executive producer Darryl F. Zanuck, contained in the Twentieth Century-Fox Produced Scripts Collection at the UCLA Arts-Special Collections Library, the three leading female roles were originally conceived for Betty Grable, Virginia Gilmore and Gene Tierney (or Arline Judge). Both John Payne and Dana Andrews were under consideration for leading roles.
Hollywood Reporter news items add the following information about the production: Robert Ellis and Helen Logan were to work on the screenplay, but the extent of their contribution to the completed picture has not been determined. Joan Davis was cast in early March 1941, although she does not appear in the picture. In late March 1941, Laird Cregar was replaced by George Lessey in the role of "William Bolton" due to Cregar's illness. Shortly after production began, Lynn Bari was replaced by Cobina Wright, Jr. in the role of "Connie Fentress" when Bari was reassigned to Sun Valley Serenade. Lessey was borrowed from M-G-M and Robert Cummings was borrowed from Universal for the production. Monica Bannister and Bunny Hartley were cast, but their appearance in the released film has not been confirmed.
According to the film's onscreen credits, the following sequences were shot on location: puddle jumping at Cypress Gardens, Winter Haven, FL; underwater and diving bell at Silver Springs, FL; underwater scenes at Rainbow Springs, Ocala, FL. Hollywood Reporter news items noted that the studio originally intended to shoot the majority of the film on location in Miami, but that "continued bad weather in Florida" forced the studio to film only background and second unit scenes there. Moon Over Miami marked the first screen appearance of noted dance director Hermes Pan, although he was supposed to have appeared in a dance number with Fred Astaire in an earlier 1941 film, Second Chorus (see below). According to modern sources, it is possible that Pan had previously appeared onscreen as a double for Astaire in long shots. Moon Over Miami also marked the screen debut of Jack Cole and his dancing company.
Twentieth Century-Fox first filmed Powys' play in 1938 as Three Blind Mice, a non-musical version directed by William A. Seiter and starring Loretta Young, Joel McCrea and David Niven (see AFI Catalog of Feature Films, 1931-40; F3.4602). In 1946, the studio produced Three Little Girls in Blue, a musical version of the play directed by Bruce Humberstone and starring June Haver and George Montgomery (see below).