To assess cortical activity during pain perception, regional cerebral blood flow (rCBF) studies were done in humans using single photon emission computed tomography (SPECT) with the radiotracer Tc99m-HMPAO and magnetic resonance imaging localization. Normalized SPECT data were analyzed by region of interest and change distribution. Contralateral somatosensory rCBF was decreased when the digits of the hand were immersed in a hot water bath for 3 min which was rated as moderately painful (persistent pain). No decrease was observed when the hand was immersed in tepid water (control). In contrast, cortical rCBF was increased during vibratory and sensorimotor tasks, in the contralateral somatosensory and sensorimotor areas, respectively. These results indicate that pain perception in man is associated with somatosensory cortical inhibition.