All pain is unpleasant, but different perceptual and emotional qualities are characteristic of pain originating in different structures. Pain of superficial (cutaneous) origin usually is sharp and restricted, whereas pain of deep origin (muscle/viscera) generally is dull and diffuse. Despite the differences it has been suggested previously that all pain is mediated by an invariant set ("neuromatrix") of brain structures. However, we report here, using functional magnetic resonance imaging (fMRI), that striking regional differences in brain activation patterns were the rule. Signal differences were found in regions implicated in emotion (perigenual cingulate cortex), stimulus localization and intensity (somatosensory cortex) and motor control (motor cortex, cingulate motor area). Further, most fMRI signal changes matched perceived changes in pain intensity. These findings clearly indicate that distinct neural activity patterns in distinct sets of brain structures are evoked by pain originating from different tissues of the body. Further, we suggest that these differences underlie the different perceptual and emotional reactions evoked by deep versus superficial pain.