This study examined brain areas involved in tonic pain perception. Cerebral blood flow was assessed by dynamic Xenon-133 inhalation single-photon emission tomography (SPET) in 7 healthy right-handed male volunteers undergoing the cold pressor test (CPT). In single experimental sessions, each subject was scanned twice, once in the resting state and once while immersing the left hand in freezing water (0 degrees C +/- 1). Immersion of the hand induced severe pain (visual analogue scale: 6.9 +/- 1.9) in all subjects. After correction for pCO2, cerebral blood flow was analyzed by placing a template of square regions of interest (ROIs) over 5 selected tomographic slices. Relative to the resting-state values, during the CPT, flow determinations revealed a 7-8% regional blood flow increase in the contralateral frontal lobe and bilateral temporal regions and a 15% flow increase in a ROI located over the primary sensorimotor cortex in the tomogram at 80 mm above the orbito-meatal line (corresponding to the cortical somatotopic representation of the hand) contralateral to the stimulated side. The tonic pain induced by the CPT thus appears to activate the contralateral frontal and bilateral temporal regions and more prominently, the primary sensorimotor cortex. This pattern of activation suggests that tonic painful stimuli activate the cortex partly via complex circuits and partly via direct somatosensory pathways.