What does the title Of Mice and Men mean?

The title Of Mice and Men symbolically represents the way mankind seeks to destroy those who seemingly hold no value within society. Mice represent those who are looked upon with scorn, much as Lennie is. It also relates to the Robert Burns quote “The best laid schemes o’ Mice an’ Men / Gang aft agley [go awry],” which is indeed the case in this novel. It suggests, too, that the concerns of mice and men are of equivalent importance.

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The title Of Mice and Men has a lofty, epic quality which initially appears at odds with the humble people Steinbeck describes. It is based on the lines in "To a Mouse" by Robert Burns:

The best laid schemes o’ Mice an’ Men
Gang aft agley,
An’ lea’e us nought but grief an’ pain,
For promis’d joy!
The author not only translates Burns's Scots into standard English, but begins with the word "of," suggesting an essay or a philosophical treatise. Whereas the poet's observation is that the plans of mice and men frequently go awry, Steinbeck's title omits the subject, suggesting that his book is a general discussion about the nature of mice and men. This intensifies the link between the two subjects. Burns suggests one thing mice and men have in common: their plans often go wrong. To write a book connecting the two species, however, would require more of a connection than this. The fate of men is of no more cosmic concern than that of mice.
Steinbeck is a laconic writer, extracting much meaning from few words. The title, Of Mice and Men, is a remarkable demonstration of his method. This is a story that connects mice with men in discussing their destinies. It does so in a systematic way, pointing out various correspondences between the two, and thereby denying any special place for humanity in the cosmos. The phrase has an epic grandeur about it, though the words are plain and simple. The author's perspective is detached as he looks at his characters, and he writes about them as characteristic specimens of their type. All this meaning can be inferred from a title of four brief words.
Last Updated by eNotes Editorial on December 8, 2020
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Other educators have commented on the connection between the title of this book and the poem by Burns, but there is also some symbolic meaning behind the title.

Mice are not valued much in society. They are often seen as a nuisance, and mankind often seeks to destroy them. Lennie recognizes that mice aren't just an object of scorn and that they have redeeming qualities, too. He enjoys petting their soft fur and finds them a gentle source of comfort. Lennie appreciates mice as much as he appreciates other innocent creatures, such as rabbits and puppies.

Lennie is much like a mouse in this regard. He has an intellectual disability, and most of mankind doesn't value his existence. He is verbally insulted numerous times in the novel, and even George, who is his closest friend, makes comments like, "If I was a relative of yours I'd shoot myself." Because of his differences, Lennie stands outside the world of acceptance, much like the mice he cares for.

Of Mice and Men, then, comes to illustrate the symbolism of innocence versus evil in the novel. The innocent will find themselves persecuted by those who don't care to find value in their existence. After he accidentally kills Curley's wife, Lennie is killed by the one man he believed he could always count on. The title reflects the way those who are seen as weak are exploited by mankind.

Last Updated by eNotes Editorial on December 8, 2020
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Yes, y2kfain is right in making an explicit link between mice and men. Both in the play are shown to be immensely fragile and breakable. Lennie with his mice unfortunately foreshadows the failure at the centre of the play. Just as Lennie wants to pet the mice and keep them as pets, he accidentally and non-intentionally kills them. In the same way, George and Lennie desperately try to achieve their dream of "living of the fatta the land", but, despite their efforts, it ends in tragedy. In such a world our plans often come to naught.

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The "Men" in the title of OF MICE and MEN refer to the common men who work on the ranch. For example, Slim, Candy, etc have simple desires and they are laborers. They want to obtain their own land so that they may work for themselves and obtain independence. The "Mice" in the title are an example of symbolism. Lennie loves mice, yet he pets them too hard and then they die. His fate in the book mirrors the fate of the mice he takes care of then kills accidently. Similiarly, George takes care of Lennie, yet he has to kill him intentionally. Both mice and men are fragile in regards to nature and the cruelties of humanity.

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The significance of the title is in the futility of planning and the inevitablility of failure if the odds are stacked against you - as they are for George and Lennie. The novel is a condemnation of the American Dream, as has been said before but it also reflects on some of the principles of the American Constitution. All men are not created equal in the eyes of humanity, and characters like Lennie and George will always be judged by his weaknesses rather than his strengths.

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The title Of Mice and Men is in reference to Robert Burns' poem.  The full phrase is "the best laid plans of mice and men often go awry."  I would look at the literal meaning of this quotation and apply it to the novel as a whole.

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The title is from the Robert Burns poem, "To A Mouse, On Turning Up Her Nest."  The speaker observes a mouse whose carefully laid home is upturned by the cruel winter winds and bitter cold.  Despite all of the mouse's hard work, her efforts are for naught: "The best-laid schemes o' mice an 'men  / Gang aft agley," the poet writes (ie, often go awry.)

Likewise, Lennie and George's plans for a life of ease an "livin' off the fatta the lan'" also are forever disrupted by Lennie's accidental murder of Curley's wife.   Like the mouse, neither could have foreseen the drastic turn their lives would take, despite their plans for the future. 

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