Effects of peripheral administration of 5-HT (5-hydroxytryptamine, serotonin) on hyperphagia induced by 2-deoxy-D-glucose(2-DG) were studied in rats. It was found that 5-HT i.p. reduced 2-DG-elicited feeding in rats dose-dependently. The 5-HT-induced hypophagia was antagonized by the 5-HT_2A receptor antagonist, ketanserin. It is known that 2-DG induces glucoprivation, resulting in hyperphagia and hyperglycemia. However, 5-HT did not affect hyperglycemia induced by 2-DG. These results suggest that peripheral injection of 5-HT reduces 2-DG-induced hyperphagia mediated by the peripheral 5-HT_2A receptor and that its effects are not due to enhancement of hyperglycemia.