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Dance director Aida Broadbent's name is misspelled "Ada" in the onscreen credits. According to Hollywood Reporter news items, Sol C. Siegel was originally scheduled to produce this picture, and Paul Yawitz was to work on a treatment of the story. Yawitz' contribution to the finished picture has not been determined, however. Hollywood Reporter news items also reveal that Carole Landis and Jane Frazee were sought for leading roles, and that Emmett Lynn was scheduled to be in the cast. Susan Hayward was borrowed from Paramount for the film. Hollywood Reporter production charts and news items include Wela Davis, Betty Blythe and Michael Morris in the cast, but their appearance in the completed film has not been confirmed. The Hollywood Reporter charts also list Joseph August as film's photographer, although all other contemporary sources credit Jack Marta. According to the The Exhibitor review, the songs "Horray for the Little Guy" and "I Went and Fell for You" were included in the film, but no other contemporary source lists them.
Information in the MPAA/PCA Collection at the AMPAS Library reveals that the Hays Office was at first reluctant to approve the film's script due to the sequence in which "Sis" performs in the burlesque house and appears to be doing a strip-tease. After producer Robert North consulted with Hays Office officials, Republic agreed to make clear that "Sis" was an unwilling participant in the disrobing sequence, and that she would be left standing in her slip. After the film was completed, the Hays Office was seriously displeased about "several breast shots," and awarded a PCA certificate only because of "the utter impossibility of deleting these shots without re-assembling [the actors and crew] and re-editing much of the footage." Republic agreed to delete "one of the two sweater shots" from prints in circulation, as well as the line "started in Flushing and ran it into a chain." Several reviews applauded the inclusion of a "gag" in which Jerry Colonna, upon getting out of a bathtub, reveals that he is dressed in an old-fashioned bathing suit and states "The Hays Office insisted."
According to contemporary sources, screen rights to the play cost $50,000 and the film cost between $200,000 and $350,000 to produce, with an advertising budget of $100,000, very large expenditures for Republic at that time. A May 2, 1941 Hollywood Reporter news item announced that the picture was "headed for Republic's first million dollar gross." The film's premiere in Saint Louis, Missouri, was a benefit for Greek War Relief. The character of Sis Hopkins, as portrayed by Rose Melville, first appeared in the theatrical play Zeb in the late 1800s. In 1894, Melville recreated the role in another play, Little Christopher, and eventually built a vaudeville sketch around Sis called "Sis Hopkin's Visit." The continued popularity of the character then prompted Melville to have a three-act theatrical play, Sis Hopkins, written for her. Melville played Sis in a Kalem short film in 1916 called She Came, She Saw, She Conquered, and acted as a consultant to Mabel Normand, the star of Goldwyn Pictures Corp.'s 1919 version of the play, also entitled Sis Hopkins, which was directed by Clarence G. Badger and co-starred John Bowers (see AFI Catalog of Feature Films, 1911-20; F1.4059).