Best friends Lennie and George find themselves unemployed in Depression-era California, unable to maintain a stable working pattern for long because of Lennie's infantile mental capacity. They soon get hired at the Tyler Ranch, working under the strict supervision of Curley, the boss's mean-spirited son. But after settling in and making friends, their world is ripped apart by tragedy when Curley's beautiful but unhappy wife becomes the innocent victim of Lennie's compassion.