Brain activity was studied with functional magnetic resonance imaging (fMRI) following thermal stimulation. Two groups (n = 6/group) of human male volunteers were given up to four noxious (46 degrees C) and four non-noxious (41 degrees C) stimuli. In the 46 degrees C experiment, positive signal changes were found in the frontal gyri, anterior and posterior cingulate gyrus, thalamus, motor cortex, somatosensory cortex (SI and SII), supplementary motor area, insula, and cerebellum. Low-level negative signal changes appeared in the amygdala and hypothalamus. All regions activated by 46 degrees C were also activated by 41 degrees C. However, except for SI and thalamus, significantly more activation was observed for the 46 degrees C stimulus. A significant attenuation of the signal change was observed by the third stimulus for the 46 degrees C, but not for 41 degrees C experiment. Similar findings were replicated in the second group. These fMRI findings specify differences between somatosensory and pain sensation and suggest a number of rich avenues for future research.