The element of surprise, a necessary condition for the experience of humor, often derives from the fact that the alternative interpretation/resolution offered by the punch line of a joke is physically or socially forbidden. Children's humor typifies violation of physical norms, whereas adult humor typically pushes the boundaries of social norms. Excess norm violation, to the point of offending, can attenuate the experience of humor/mirth. To examine the neural basis of regulation of affective experience of humor by social norms, we scanned 16 normal subjects while they viewed a series of cartoons that varied in funniness and social acceptability. Behavioral results indicated two separate groups of subjects, those who found the cartoons less offensive and those who found them more offensive. In the group that found the jokes more offensive, there was a negative correlation between funniness and social inappropriateness. In this group, the corresponding Humor by Social inappropriateness interaction during functional magnetic resonance imaging revealed enhanced activation in the right hippocampus along with relative deactivation in the ventral medial prefrontal cortex (VMPFC). By contrast, the Funniness by Social appropriateness interaction resulted in activation in the VMPFC and relative deactivation in the right hippocampus. These results suggest that the regulation of humor by social norms involves reciprocal response patterns between VMPFC and hippocampus regions implicated in contextual regulation of behavior and memory, respectively.