Functional magnetic resonance imaging and echo-planar-imaging were used to investigate affect related gender differences in regional cerebral activity. The experiment was conducted using a standardized mood induction procedure. Blood-oxygen-level-dependent effect was measured in 13 male and 13 female healthy subjects, during both moods of happiness and sadness, respectively. Parallel to earlier neuroimaging findings, our results show brain activity in the amygdala of males during negative affect. Females failed to demonstrate a similar activation pattern despite matched subjective ratings of negative affect to males. Results point to differential regional cerebral correlates of emotional experience in males and females, which is suggestive of a more focal and subcortical processing of sadness in men.