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According to the Twentieth Century-Fox Produced Scripts Collection, located at the UCLA Arts-Special Collections Library, Robert Hopkins, Len Hammond and Jo Swerling worked on early versions of this film's screenplay. Their work was not included in the final picture, however. Late 1941 Hollywood Reporter news items reported that Ken Englund and Harold Friedman had been assigned to work on the script, but their contribution to the completed film appears doubtful. According to a March 10, 1942 Hollywood Reporter news item, writer Richard Macauley was being considered to direct the picture. An September 11, 1942 Hollywood Reporter news item noted that producer Milton Sperling was leaving the studio to join the Marines, and that his duties would be assumed by Lee Marcus. Hollywood Reporter production charts list William Perlberg as the film's producer, and it is possible that either he or Marcus supervised the film during shooting, although Sperling receives sole onscreen credit as the producer.
According to a June 20, 1941 Hollywood Reporter news item, Gene Tierney was set for a top role in the picture. A February 6, 1943 Los Angeles Times item reported that Carole Landis and Betty Grable would be the film's stars, while a February 10, 1942 Hollywood Reporter item noted that Anne Baxter had been set in the picture. Other Hollywood Reporter news items include Reginald Gardiner and Harry Green in the cast, but they did not appear in the released picture.
Although a November 27, 1942 studio press release announced that newspaper columnist Harry Crocker would appear in the film playing one of his own ancestors, who were socially prominent bankers in San Francisco, his appearance in the completed picture has not been confirmed. As noted by studio publicity, technical advice about turn-of-the-century San Francisco was provided by showman Sid Grauman, the owner of the renowned Chinese Theatre in Hollywood. The picture marked the return to the screen of Alice Faye, who had taken time off to have her first child following filming of Week-End in Havana in 1941, and the last film appearance of John Payne, who joined the Army Air Corps, until the 1945 picture The Dolly Sisters. According to a modern source, "I Gotta Have You," a song composed by Mack Gordon and Harry Warren, was recorded for the picture but cut before its release. Gordon and Warren received an Academy Award for Best Original Song for "You'll Never Know," which became Faye's signature song.
According to Hollywood Reporter news items, San Francisco mayor Angelo Rossi met with studio executive Joseph Schenck in February 1943 to protest the use of the nickname "Frisco" in the film's title. Armed with petitions from several prominent civic organizations, Rossi persuaded Schenck to change the film's title to Hello, San Francisco, Hello in all its advertising in that city. Laurence Hirsch, the executor of the estate of composer Louis A. Hersch, who co-wrote "Hello, Frisco, Hello" with Gene Buck, brought an infringement suit against two music publishers and Twentieth Century-Fox, claiming that they did not have the right to use the song in the picture. His suit was dismissed in June 1945, however. Conductor and musician Pietro Cimini filed a lawsuit against the studio in 1943, in which he claimed that he was ridiculed and defamed, according to a May 1943 Daily Variety news item. Referring to the scene in which "Johnny" closes the opera house, thereby enraging a musician character named "Chambinni," Cimini asserted that the film depicted him as "inefficient and incompetent." The disposition of Cimini's suit has not been determined.
Faye recreated her role in the November 15, 1943 Lux Radio Theatre presentation of the story, which co-starred Robert Young. Hello Frisco, Hello is an uncredited remake of the 1936 Twentieth Century-Fox film King of Burlesque, which was also based on Via Delmar's original, unpublished story entitled "The Day Never Came." The 1936 film was directed by Sidney Lanfield and starred Faye, Warner Baxter and Jack Oakie (see AFI Catalog of Feature Films, 1931-40; F3.2291).