through the whole story
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The fact that an intelligent man like George travels with a mentally challenged guy like Lennie is considered, by many, to be ironic. THere are many more as well:
-Lennie's last name is Smalls yet he is a big powerful guy.
-At the end of the book George is forced to kill the person he loves the most out of kindness (the other men were coming to lynch Lennie)
-George complains about Lennie but without Lennie he is just another lonely farm hand.