正如他们自豪地宣称的那样，主角乔治和伦尼与众不同，因为他们拥有彼此。他们是一对奇怪的夫妇，乔治，精明，结实，但最终还是很有同情心的保护者，他的名字叫Lennie Small，讽刺的是，Lennie Small，实际上是一个巨人，他不知道自己的力量，在精神上不能为自己做最小的决定;他完全依赖乔治，但同样，乔治需要伦尼，因为他给了他一个继续前进的理由。伦尼虽然智力低下，却能感觉到这一点，因为当他知道乔治因为生他的气而感到内疚时，他利用这一时刻操纵乔治重复他们“梦想的未来”的故事，尤其是他们打算养的兔子，而伦尼对此非常着迷。他们没有亲戚关系，但伦尼的姑姑把乔治养大了，他答应过她，他会照顾伦尼，现在她死了。的秘密他们分享的梦想,生活在一个农场和“丽芙·(ing) fatta局域网的中央,但这本书的标题,从罗伯特·彭斯的诗“鼠标”预示着他们梦想的最终失败,因为它说的计划出了问题。这两名男子正在前往另一个从事一系列农场工作的路上，他们之前居住和工作的地方杂草已经被用完，因为伦尼被错误地指控试图强奸，因为他天真地希望触摸女孩裙子的布料;这也为小说的悲剧结局埋下了伏笔。事实上，整本书都遵循了小说开头设定的循环运动，以及在结尾中所使用的相反的描述，故事发生在同一个地点，Lennie被警告如果出了什么问题就回来，这是不可避免的。
The central protagonists, George and Lennie are, as they are proud to proclaim, different from the others because they have each other. They are an odd couple, George the shrewd, wiry yet ultimately caring protector of the ironically named Lennie Small, who is, in fact, a huge man who doesn’t know his own strength and is mentally incapable of making the smallest of decisions for himself; he relies on George completely but equally, George needs Lennie as he gives him a reason to keep going. Lennie, despite his lack of intellect, senses this because when he knows George feels guilty for being angry with him, he takes advantage of the moment to manipulate George into repeating the story of their ‘dream future’, especially the rabbits they intend to keep with which Lennie is obsessed.They are not related but Lennie’s aunt has brought up George and he has promised her that he will look after Lennie, now she has died. The secret dream they share, of building a life together on a ranch and ‘liv[ing] off the fatta the lan’ is central but the very title of the book, taken from Robert Burns’ poem ‘To a Mouse’ foreshadows the ultimate defeat of their dream, since it speaks of plans going wrong.The two men are en route for another in a series of ranch jobs, having been run out of Weed, the place where they previously lived and worked, because Lennie has been wrongly accused of attempted rape because of his innocent desire to touch the material of a girl’s skirt; again there is foreshadowing here of the tragic ending of the novel. Indeed, the whole of the book follows the circular movement established by the setting of the beginning of the novel and inverting descriptions used there in the ending which takes place in the same spot, where Lennie has been warned to return if anything goes wrong which inevitably it does.