Curley, one of the antagonists from John Steinbeck's novel Of Mice and Men, picks a fight with Lennie. Lennie is, by far, one of the largest (and perhaps strongest) men on the farm.
One could justify that Curley chooses to pick a fight with Lennie because he recognizes the fact that Lennie is simply not all there. Curley, like many of the other men, can tell that something is "wrong" with Lennie. When first questioned by Curley, George continuously answers questions for both himself and Lennie. When Curley asks about Lennie talking, Lennie looks funny.
Lennie was looking helplessly to George for instruction.
A man looking helpless is one sign of weakness. It is certain that Curley saw Lennie's look as one of weakness and believed the he would be able to fight him with no problem.
Unfortunately for Curley, he has underestimated Lennie. While Curley mistakes Lennie's mental slowness for physical weakness, Lennie shows him that one does not necessarily equate the other.
Later in chapter three, when the fight between the men happens, Lennie's initial reaction to Curley shows weakness.
Lennie looked helplessly at George, and then he got up and tried to retreat. Curley was balanced and poised. He slashed at Lennie with his left, and then smashed down his nose with a right. Lennie gave a cry of terror. Blood welled from his nose. "George," he cried. "Make 'um let me alone, George."
In the end, Curley simply refuses to think that he is unbeatable. He is known around the ranch as a man no one should mess with. Unfortunately for Curley, Lennie is simply too slow (mentally) to realize this.
Slim wants to pick a fight with Lennie because he sees that Lennie is mentally impaired and he wants to use Lennie's mental issue to his advantage