- George Milton: A quick-witted man who is Lennie's guardian and best friend. His friendship with Lennie helps sustain his dream of a better future. He has been friends with Lennie since they were children. He is described by Steinbeck in the novel as "small and quick", every part of him being "defined", with small strong hands on slender arms. He has a dark face and "restless eyes" and "sharp, strong features" including a "thin, bony nose".
- Lennie Small: A gigantic, physically strong imbecile who travels with George and is his constant companion.[5] He dreams of "living off the fatta' the lan'" and being able to tend to rabbits. His love for soft things is a weakness, mostly because he does not know his own strength, and eventually becomes his undoing. Steinbeck defines his appearance as George's "opposite", writing that he is a "huge man, shapeless of face, with large, pale eyes" and "wide, sloping shoulders". Lennie walks heavily, dragging his feet a little, "the way a bear drags his paws", adding that his arms do not swing at his sides, but hang loosely.
- Candy: An aging ranch handyman, Candy lost his hand in an accident and worries about his future on the ranch. Fearing that his age is making him useless, he seizes on George's description of the farm he and Lennie will have, offering his life's savings if he can join George and Lennie in owning the land.
- Slim: A "jerkline skinner", the main driver of a mule team and the "prince of the ranch". Slim is greatly respected by many of the characters and is the only character whom Curley treats with respect. His insight, intuition, kindness and natural authority draw the other ranch hands automatically towards him, and he is significantly the only character to fully understand the bond between George and Lennie. Slim is considered the "übermensch"[6] of this story by the god-like descriptions of Slim that he is the one that knows best out of the novel’s characters.
- Curley: The Boss's son, a young, pugnacious character, once a semi-professional boxer. He is described by others, with some irony, as "handy", partly because he likes to keep a glove filled with vaseline on his left hand. He is very jealous and protective of his wife and immediately develops a dislike toward Lennie. At one point, Curley loses his temper after he sees Lennie appear to laugh at him, and ends up with his hand horribly damaged after Lennie fights back against him.
- Curley's wife: A young, pretty woman, who is mistrusted by her husband. The other characters refer to her only as "Curley's wife". Steinbeck explained that she is "not a person, she's a symbol. She has no function, except to be a foil – and a danger to Lennie."[5] Curley's wife's preoccupation with her own beauty eventually helps precipitate her death: She allows Lennie to stroke her hair as an apparently harmless indulgence, only for her to upset Lennie when she yells at him to stop him "mussing it". Lennie tries to stop her yelling and eventually kills her accidentally by breaking her neck.
- Crooks: Crooks, the black stable-hand, gets his name from his crooked back. Proud, bitter, and cynical, he is isolated from the other men because of the color of his skin. Despite himself, Crooks becomes fond of Lennie, and though he claims to have seen countless men following empty dreams of buying their own land, he asks Lennie if he can go with them and hoe in the garden. Crooks is a more relatable individual who sees things from a more rational and human perspective.
- Candy's dog: A blind dog who is described as "old", "stinky", and "crippled", and is killed by Carlson.
- Carlson: A "thick bodied" ranch hand, he kills Candy's dog with little sympathy.
- The Boss: Curley's father, the superintendent of the ranch. The ranch is owned by "a big land company" according to Candy.
- Whit: A young ranch hand.
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