- Al Mulock, who played one of the three gunmen in the opening sequence, committed suicide on the set.
- Henry Fonda originally turned down a role in the picture. Director Sergio Leone flew to the United States and met with Fonda, who asked why he was wanted for the movie. Sergio replied, "Picture this: the camera shows a gunman from the waist down pulling his gun and shooting a running child. The camera pans up to the gunman's face and... it's Henry Fonda."
- The credits, concluding with Director Sergio Leone, last over ten minutes into the start of the film.
- Harmonica, Frank, and Cheyenne.
- Henry Fonda prepared for his role as the villain "Frank" by arriving in Italy with a pair of brown colored contact lenses. When Sergio Leone saw them, he ordered them removed. Leone had planned an important close-up shot of Fonda and wanted those blue eyes.
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