To elucidate the mechanism of general anesthesia, effects of sevoflurane anesthesia on serotonin metabolism in rat brain were studied. Three percent sevoflurane was administered for twenty minutes to Wistar male rats weighing 230-270g under spontaneous respiration. The rats were sacrificed by decapitation and the brains were rapidly removed. They were dissected into nine discrete regions, locus coeruleus, pons plus medulla oblongata, hypothalamus, thalamus, basal ganglia, midbrain, hippocampus, amygdala and cerebral cortex. The contents of serotonin (5-HT) and one of its major metabolites, 5-hydroxyindole-3-acetic acid (5-HIAA) were measured by high performance liquid chromatography with the dual-cell coulometric detector before anesthesia, 20 minutes after the start of anesthesia and at the recovery from anesthesia. Significant increases in 5-HT levels were observed in the pons, hypothalamus, midbrain, amygdala and cerebral cortex by sevoflurane anesthesia as compared with the control group. 5-HIAA levels decreased significantly in the thalamus by sevoflurane anesthesia, while an appreciable increase in 5-HIAA levels was observed in the basal ganglia at the recovery from anesthesia. It is concluded that 5-HT metabolism is significantly suppressed in the pons, hypothalamus, thalamus, midbrain, amygdala and cerebral cortex during sevoflurane anesthesia and this change in 5-HT metabolism may be associated with a mechanism of sevoflurane anesthesia.