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Individuals differ in the extent to which they experience negative mood states over time. To explore the relationship between individual differences in negative affect (NA) and brain activity, we asked healthy subjects participating in positron-emission tomography scans to rate the extent to which they had experienced NA terms during the month before scanning. In two independent samples of subjects, resting regional cerebral blood flow within the ventromedial prefrontal cortex (VMPFC) correlated with ratings of NA. The finding converges with recent evidence implicating the VMPFC in emotional and autonomic processing. Moreover, it demonstrates that variability in basal VMPFC activity across subjects is related to individual differences in subjective emotional experience.