Touching warm and cool bars that are spatially interlaced produces a painful burning sensation resembling that caused by intense, noxious cold. We demonstrated previously that this thermal grill illusion can be explained as an unmasking phenomenon that reveals the central inhibition of pain by thermosensory integration. In order to localize this unmasking in the human brain, we have used positron emission tomography (PET) to compare the cortical activation patterns evoked by the thermal grill and by cool, warm, noxious cold and noxious heat stimuli. The thermal grill illusion produces activation in the anterior cingulate cortex, whereas its component warm and cool stimuli do not. This area is also activated by noxious heat or cold. Thus, increased activity in the anterior cingulate cortex appears to be selectively associated with the perception of thermal pain. Disruption of thermosensory and pain integration may account for the central pain syndrome that can occur after stroke damage.