What significance does the title Of Mice and Men have?

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I would also suggest that the title may be a double entendre, alluding to the fact that Lennie likes to keep wild mice as pets and that he gets pleasure out of stroking their soft fur but always ends up killing them, not accidentally but on purpose. 

"They was so little," he said, apologetically. "I'd pet 'em, and pretty soon they bit my fingers and I pinched their heads a little and then they was dead--because they was so little."

This interest in mice shows, among other things, that Lennie is becoming more self-assertive. He lies about having the mouse. He complains about George taking it away. He threatens to run away and live by himself in a cave. George seems to be having increasing difficulties making Lennie obey him. Lennie's interest in petting soft little animals also foreshadows a growing interest in sex. He got them both in serious trouble by grabbing a girl's dress in Weed, and he shows a strong interest in Curley's wife, who he later kills "accidentally" to prevent her from struggling and screaming. It is Lennie who spoils the "best laid plans" of the two men to own a little farm.

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The title of Of Mice and Men is taken from a poem written by the Scottish poet, Robert Burns, in 1785, called "To A Mouse." The following lines of this poem are highly significant in illuminating the novel's key themes (a translation is provided in brackets):

The best laid schemes o' Mice an' Men, [The best laid plans of mice and men],

Gang aft agley, [Often go wrong],

An' lea'e us nought but grief an' pain, [And leave us nothing but joy and pain],

For promis'd joy! [For promised joy!]

Like Burn's mouse, George and Lennie have a dream for their future: to own their own piece of land and run their own farm, as George comments in Chapter One:

Someday—we're gonna get the jack together and we're gonna have a little house and a couple of acres an' a cow and some pigs. 

But once the men find work on Tyler Ranch, their dream begins to unravel, just like the plans of the mouse in Burns' poem. Their conflicts with Curley and the (accidental) death of Curley's wife have a dramatic and enduring impact on the two men and the course of their lives. 

In this understanding, then, Steinbeck has deliberately taken the title from this quote because it symbolizes the destruction of the American Dream and sends the important message that, sometimes, things go wrong and there is nothing you can do to stop that from happening. 

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