Lennie (John Malkovich) and George(Gary Sinise) are life long friends who wander the country looking for odd jobs during the depression era. Lennie is physically strong and intimidating but is really mentally slow and sweet. George is gruff and street smart. They find themselves taking a labor intensive job as field hands to hopefully save enough money to own a ranch. Their boss is a man named Curley (Casey Siemaszko) a mean spirited farmer. There is a great deal of tension between the field hands and Curley, who's beautiful but bored wife (Sherilyn Fenn) flirts with the men . George and Lennie try to keep a low profile but Lennie's child like mentality and strength find them in trouble. It's Lennie's relationship with Curley's wife that destroys their hopes for their future. It is George who must somehow save Lenny from a tragic fate.