Alterations of 5HT and its chief metabolite 5HIAA were studied in four regions of the rat brain following acute 1-h swim exercise and 4 week chronic swim exercise (30 min/day, 6 days per week). Acute exercise significantly increased the synthesis and metabolism of 5HT in brain stem. Hypothalamus also showed increased levels of 5HT. However, no changes were observed in the cerebral cortex and hippocampus. Chronic exercise activated not only the synthesis but also the metabolism of 5HT in the cerebral cortex; this neuronal adaptation was sustained even 1 week after the termination of training. In brain stem, increased 5HT turnover was observed immediately after training. In hypothalamus, decrease in 5HT and 5HIAA levels occurred immediately after training, followed by a rebound increase in their levels after 1 week posttraining rest. In hippocampus, a delayed effect was observed, because 5HT level was unaltered immediately after the training, but its turnover decreased after 1 week rest. These findings have been discussed in an attempt to explain the antidepressant effect of exercise based on the 5HT deficiency theory of endogenous depression.