Effects of serotonin (5-HT) on plasma glucose and serum insulin levels were studied in mice. In normal mice, 5-HT induced a dose-dependent hypoglycemia and an increase in serum insulin levels. 5-HT significantly inhibited glucose-induced hyperglycemia and increased glucose-stimulated insulin release. However, in streptozotocin-induced diabetic mice, 5-HT changed neither the glucose nor insulin levels. These results strongly suggest that 5-HT-induced hypoglycemia is brought on by increasing serum insulin levels.