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Production began only four weeks after John Ford finished work on Drums Along the Mohawk (1939). Because of this, most of the pre-production work was done for him ahead of time, including the hiring of Gregg Toland as cinematographer, who along with art directors Richard Day and Mark-Lee Kirk planned much of the look of the film based on a vast array of research photos and documents.
Prior to filming, producer Darryl F. Zanuck sent undercover investigators out to the migrant camps to see if John Steinbeck had exaggerated about the squalor and unfair treatment meted out there. He was horrified to discover that Steinbeck had actually downplayed what went on in the camps.
John Steinbeck loved the movie and said that Henry Fonda as Tom Joad made him "believe my own words".
John Ford banned all makeup and perfume from the set on the grounds that it was not in keeping with the tone of the picture.
John Steinbeck was particularly enamored with the performance of Henry Fonda as Tom Joad, feeling that he perfectly encapsulated everything he wanted to convey with this character. The two became good friends. Indeed Fonda did a reading at Steinbeck's funeral.
While filming the Joads' car traveling down the highway, John Ford wanted to add a shot showing the large number of caravans heading west, so the film's business manager stopped actual cars making the trek and paid the drivers five dollars to escort the Joads' jalopy for the cameras.