The setting is at a ranch in the Salinas Valley of California where two traveling workers, George Milton and Lennie Small, are on their way to a California ranch. Lennie and George are two complete opposites. George is small, quick, and smart while Lennie is big, slow, and simple-minded. On their way they are walking and Lennie is carrying a dead mouse.

George always tells him he shouldn't play with small animals. Lennie likes to pet soft things, such as mice to soft dresses of women. When they get to the ranch to apply for the job George does all the talking because he knows Lennie would mess up in some way. After they are accepted for the job they are resting in their bunk, when Curly, the boss's son, enters the bunk house and tries to pick a fight with Lennie. George stands up for him and...