One of the most important foreshadowing elements of the story occurs in the first chapter when George vents his anger and frustration over the latest trouble Lennie has caused him.
"You crazy son-of-a-bitch. You keep me in hot water all the time." He took on the elaborate manner of little girls when they are mimicking one another. "Jus' wanted to feel that girl's dress--jus' wanted to pet it like it was a mouse-- Well, how the hell did she know you jus' wanted to feel her dress? She jerks back and you hold on like it was a mouse. She yells and we got to hide in a irrigation ditch all day with guys lookin' for us, and we got to sneak out in the dark and get outta the country."
Twice George compares the dress to a mouse. He doesn't realize it, but he is touching on the fact that Lennie's fondness for stroking soft little creatures has a sexual component and that it is evolving dangerously into a sexual interest in young girls. This will lead to his killing Curley's wife in the barn when he won't let go of her hair and she tries to scream. George was not present when Lennie molested the girl on the main street of Weed in broad daylight. He only knows what Lennie told him, and Lennie lies to George consistently. Besides that, Lennie does not even understand his own impulses. He has no self-control. Evidently Lennie didn't just want to feel the girl's dress, which would have been bad enough, but he may have been trying to pull it off. And the girl may have been quite young. When George realizes the truth about Lennie, after seeing the dead body of Curley's teenage wife in the barn, he decides that Lennie has become a menace to society and must be put away or killed.
"I guess I should of knew," George said hopelessly. "I guess maybe way back in my head I did."
George's diatribe against Lennie in Chapter One foreshadows that George is going to kill him sooner or later. Lennie is getting to be too much of a burden. George has trouble enough finding jobs for himself in these Great Depression times. He is worn out with the thankless task of being Lennie's caregiver and finding jobs for a retarded man. He can't be with him all the time. It is becoming an impossible situation. The reader knows there is going to be trouble when they get to the ranch tomorrow. George feels responsible for whatever Lennie does. This is understandable because George really is responsible. Curley's wife wouldn't have been killed if George hadn't talked the ranch boss into hiring Lennie.
There is a lot of foreshadowing in the opening chapter at the campsite by the river. Lennie's refusal to give up the dead mouse shows he is developing a will of his own and is becoming harder and harder for George to control. Both of these men are changing. George is getting tired of his role as Lennie's guardian, and Lennie is getting tired of being bossed around. This foreshadows an inevitable rupture of their relationship.