Abstract In view of the similarity of the cardiovascular actions of the 5-hydroxytryptamine precursor 5-hydroxytryptophan (5-HTP) and those of l-DOPA and the finding that l-DOPA reduces efferent sympathetic nerve activity, the role of sympathetic outflow in the cardiovascular response to 5-HTP was examined in the present experiments. Intravenous injection of 5-HTP (3.2 32 mg/kg) after peripheral decarboxylase inhibition, resulted in a progressive reduction in blood pressure and heart rate in anaesthetized cats. Spontaneous electrical activity of the cardiac, renal and splanchnic nerves also decreased in a dose-related fashion. More direct administration of 5-HTP, as well as 5-hydroxytryptamine, to the brain via a lateral ventricle also produced a fall in pressure, heart rate and sympathetic nerve activity. These experiments indicate that the overall actions of 5-HTP on the central nervous system result in a diminution of sympathetic outflow leading to a reduction of blood pressure and heart rate and thus resemble the effects of l-DOPA. The actions of 5-hydroxytryptamine are consistent with the hypothesis that it mediates the response to 5-HTP.