Friendship, and its scarcity among ranch workers, is a central theme in the novel. George and Lennie are unusual in traveling together and seeking work together in a period when jobs are scarce. Without any explicit reference to a possible sexual relationship, Slim remarks on their pairing, "Funny how you an' him string along together."
George takes issue with the comment and explains that the two of them knew each other back home long ago. Their friendship naturally evolved; they "Got kinda used to each other after a little while.”
For African Americans, it was more challenging not only to make friends but also to even find a welcoming atmosphere, due to racist discrimination and segregation. Crooks explains the limitations imposed on him and the toll they take:
S’pose you couldn’t go into the bunk house and play rummy ‘cause you was black. How’d you like that? S’pose you had to sit out here an’ read books. . . . Books ain’t no good. A guy needs somebody—to be near him. . . . A guy goes nuts if he ain’t got nobody. Don’t make no difference who the guy is, long’s he’s with you.
George and Lennie often acknowledge their dependence on each other. As Lennie succinctly states, "I got you to look after me, and you got me to look after you."