To elucidate the functional localization and somatotopic organization of pain perception in the human cerebral cortex, we studied the regional cerebral blood flow using positron emission tomography during selective painful stimulation in six normal subjects. Response to a painful stimulus was elicited using a special CO2 laser, which selectively activates nociceptive receptors, to the hand and foot. Multiple brain areas, including bilateral secondary somatosensory cortices (SII) and insula, and the frontal lobe and thalamus contralateral to the stimulus side, were found to be involved in the response to painful stimulation. While our data indicate that the bilateral SII play an important role in pain perception, they also indicate that there is no pain-related somatotopic organization in the human SII or insula.