To better understand the antinociceptive effect of fluvoxamine, we measured regional cerebral blood flow during laser-evoked pain and hot sensations using H(2)15O positron emission tomography and also subjective pain and hot sensations before and after fluvoxamine or placebo administration for 7 days to 12 healthy volunteers. The subjectively rated pain score was significantly reduced by fluvoxamine administration. Painful stimuli activated multiple brain regions. After fluvoxamine administration the ipsilateral anterior cingulate cortex (ACC), contralateral insular cortex (IC), and contralateral secondary somatosensory cortex (SII) activations were reduced. The bilateral IC activation was also reduced in the placebo group. These results suggest that fluvoxamine specifically reduced activation of the ACC and SII, which are areas concerned with the affective and integrative components of pain.