The remarkable Jekyll-to-Hyde transition scenes in this film were accomplished by manipulating a series of filters in front of the camera lens, filters which alternately revealed and obscured portions of Fredric March's Hyde makeup. 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.
The heavy make up he wore as Hyde almost damaged Fredric March's face.
When discussing whom to cast as Jekyll/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 (I)' 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, Jekyll/Hyde was the part that finally lead to Hollywood taking him seriously in more demanding roles.
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.
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.
Edgar Norton had first played Poole onstage in 1898.
John Barrymore, who had made a big comeback in the 1920 silent version, was offered the leading role in this film but turned it down.