A young unknown actor, Archibald Leach, was nursed to health by an older actress, Jean Adair during a theatrical tour. 20 years later, she joined Leach, now Cary Grant, in Arsenic and Old Lace.

Bob Hope was originally intended to star, but couldn’t be released from Paramount. The Broadway play, that starred Boris Karloff, performed 1,444 performances.

When the movie was planned, the two aunts and ‘Teddy’ from the play were cast. Their parts were replaced by other actors. But the play's producer would not let Karloff leave, as he was the star attracting audiences. Raymond Massey played his part made up to look like Karloff, so the line ‘He looks like Boris Karloff’, was kept in the movie.

Boris Karloff gave his permission for the use of his name in the movie. He was always a good sport, and as percentage holder of the play, he knew the movie would help bring in audiences to see him perform.

Cary Grant thought he over-acted in the comedy, so director Frank Capra promised to re-shoot some scenes. But Capra was called to serve in WW2, so it didn't happen. Grant told his daughter “E-gads, all the overwrought double takes, all the gags. I’m way over the top.” She told him, “No. It’s a hilarious, sweet, madcap, thoroughly memorable movie.”