When discussing whom to cast as Dr. Jekyll/Mr. Hyde, studio head Adolph Zukor initially suggested Irving Pichel for the part. Director Rouben Mamoulian turned it down because he wanted an actor who could play both parts convincingly, and felt Pichel could only play Hyde. Phillips Holmes was considered and rejected for the opposite reason: he would have been a good Jekyll but a poor Hyde. Mamoulian then suggested Fredric March. Zukor felt that this was a bad choice because, up till then, March had been featured in mostly lightweight roles. Mamoulian insisted that March was perfect for the part, and Zukor acquiesced. In addition to winning March the first of his two Oscars, Dr. Jekyll/Mr. Hyde was the part that finally led to Hollywood taking him seriously in more demanding roles.
The remarkable Jekyll-to-Hyde transition scenes in this film were accomplished by manipulating a series of variously colored filters in front of the camera lens. Fredric March's Hyde makeup was in various colors, and the way his appearance registered on the film depended on which color filter was being shot through. During the first transformation scene, the accompanying noises on the soundtrack included portions of Bach, a gong being played backwards, and, reportedly, a recording of director Rouben Mamoulian's own heart. Only in the late 1960's did Mamoulian reveal how they were done.
Miriam Hopkins originally turned down the role if Ivy Pearson, saying she wanted to play Muriel Carew instead. She soon changed her mind when the director informed her many actresses in Hollywood could be cast in her place.
The characters of Muriel Carew and her father do not appear in Robert Louis Stevenson's original story. They are based on similar characters created by playwright T.R. Sullivan for his 1887 stage adaptation of the story.
When Dr. Jekyll comes to Muriel Carew's house for the final time, she is playing "Aufschwung" ("Soaring") from Fantasiestuecke, Op. 12, by Robert Schumann. This is a particularly apposite choice of music for the film, because Schumann had created two alter egos reflecting two different aspects of his personality, the impetuous and passionate "Florestan" and the introverted "Eusebius." Much of his music criticism was written using one or the other as a pseudonym, and the two frequently appear in his music in one guise or another.
When MGM decided to produce their own version of "Dr. Jeckyll and Mr. Hyde" in 1941 with Spencer Tracy, they acquired the rights to the Fredric March version. In order to avoid any competition or unfavorable comparison, MGM essentially suppressed the March version, and made it unavailable for viewing for many years.