To determine if serotonin plays a role in the regulation of renin secretion, pentobarbital-anesthetized dogs were injected intravenously with drugs which modify serotonin metabolism. Renal perfusion pressure was kept constant by a clamp on the aorta proximal to the renal arteries. 5-Hydroxytryptophan (5-HTP) caused a significant increase (p < 0.05) in arterial plasma renin activity (PRA) that was abolished when peripheral and central aromatic amino acid decarboxylase activities were inhibited by administration of benserazide, but not reduced when only the peripheral decarboxylase activities were inhibited by administration of carbidopa. The serotonin receptor blocking drug metergoline also abolished the renin response to 5-HTP. L-Tryptophan in two different doses increased PRA. This increase was not reduced by carbidopa but was reduced or abolished by benserazide, metergoline, and renal denervation. The increase in PRA produced by 5-HTP and L-Tryptophan occurred without any change in blood pressure. 5-HTP had no effect on heart rate but L-Tryptophan reduced heart rate. These data indicate that 5-HTP and L-Tryptophan act on the central nervous system to produce an increase in renin secretion that is mediated via the renal nerves and occurs without a concomitant increase in sympathetic output to the heart or blood vessels. The increase appears to be due to the release of serotonin within the central nervous system.