What is the meaning and significance of the last line in Of Mice and Men:"Now what the hell do you suppose is eatin' them two guys?"
Curly and Carlson say this after George kills Lennie. What does it signify?
Clearly, Carlson's callousness, shown earlier in the novella, Of Mice and Men is again evinced in his remark to Curley after Carlson is too late to shoot Lennie with his Kruger. Just as he has had no feeling for Curley's old dog, thinking nothing of shooting the animal because "he stinks," and is no longer useful, Carlson has no pity or feelings of any kind for George, who Slim consoles. In fact, Carlson exemplifies what George has told Slim earlier in Chapter 3: men who
"go around on the ranches alone....after a long time...get mean."
This disparity between the reactions of George, who has lost his friend and the dream of their owning a ranch together, and Slim, who hears more than is said and understands so much with his "God-like eyes" is sharply apparent at the end of Steinbeck's novella. The brutal and callous like Carlson and Curley will never comprehend the fulfillment of the fraternity of men that Lennie, George, and Candy understood. And, because of this incomprehensible callousness, men will remain alienated and solitary.
The fact that Carlson has no idea what is "eating them guys" suggests a few things. Not only is Carlson callous, as mwestwood has described above, but his lack of insight also indicates that George will not be caught for the crime he has committed.
At this point in the novel not only has Lennie killed someone, but George has, too. George's act of killing is arguably justified, but it is only justified by what he knows (and what Slim surmises).
Slim understands that Lennie has probably killed before. When Curley's wife's body is discovered and George sees that it was Lennie who killed her, Slim connects the dots. George nods when Slim suggests that Curley's wife's death is "like that time in Weed you was tellin' about."
Only George and Slim understand that George has killed Lennie to put an end to the danger he poses to others. Carlson believes that George has killed Lennie for the same reason that Curley would have or that he (Carlson) would have -- as retribution for the death of Curley's wife.
Thus when Slim says "A guy got to sometimes" as a way to soothe George after killing Lennie, there is a recognition that George has killed his best and only friend and that George will have to live the guilt of this act. Despite the idea that this action was justified, George is now implicated in Curley's wife's death. Had he stopped Lennie earlier by turning him in to the authorities for what happened in Weed, Curley's wife would still be alive.
George's guilt then is double. He has let someone be hurt by Lennie and has been forced to kill his friend as a result.
"The grief he feels over the necessity of killing Lennie is also evidence of George's essential decency" (eNotes).
What is "eating" George is highly personal and, because people like Carlson do not understand, will remain a personal guilt and a grief that he will have to find a way to live with.