Serotonin (5-HT) and 5-hydroxyindolacetic acid (5-HIAA) were determined in seven brain regions of semistarved and control male rats. After semistarvation on a high carbohydrate diet serotonin turnover, as indicated by 5-HIAA/5-HT ratio, was increased in the total brain and several regions both three and 24 hours after the last meal. In contrast, after semistarvation on a high-protein diet serotonin turnover was decreased three hours after ingestion of the final meal, but increased 24 hours thereafter. Compulsary running wheel activity for one hour did not influence diet induce changes in serotonin turnover. Alterations in plasma corticosterone during semistarvation were not related to changes in central serotonin turnover. Data suggest that the interaction of caloric restriction and diet composition determines serotonin turnover during semi-starvation.