At the time of production, Warner Bros. announced that the Brewster house was the largest set ever built at the studio. The house was complete, room by room, in every detail. Production records confirm that several scenes were shot in various rooms of the Brewster house. (Mortimer's grandfather's study, the aunts' bedroom, and the cellar were filmed, but not included in the final cut of the film).
Cary Grant's birth name, Archie Leach, appears on a tombstone in the cemetery near the Brewster's house. In Grant's earlier picture, La dame du vendredi (1940), his character, Walter, responded to a threat by saying 'Listen, the last man that said that to me was Archie Leach, just a week before he cut his throat'. As a gag, the departed Mr. Leach was apparently interred in the Brooklyn cemetery by the Brewster's home.
On stage, Boris Karloff played the monstrous Jonathan Brewster, Raymond Massey's film character, who, in eerie-looking screen makeup, resembled Karloff, which was a running gag throughout the film. Karloff eagerly wanted to do this film, but he was kept under contract by the Broadway play producers and wasn't allowed to do the picture, to his immense displeasure. (Almost 2 decades later, he did get a chance; in the TV version, Arsenic & Old Lace (1962), and his wish came true).
According to "Dear Boris" biographer Cynthia Lindsay, Josephine Hull and Jean Adair went to their graves believing that Boris Karloff had been so saintly as to agree to let them go to Hollywood to make this film while he stayed on Broadway doing the play. Nothing could have been further from the truth: Karloff was very angry and disappointed that he was the only cast member not allowed out of his contract to do the film.
Frank Capra related to the role of Mortimer, in the film, because, like that character, he also had an older brother who abused him as a child and grew up to be a criminal.