We investigated the influence of melatonin on the human autonomic functions by measuring muscle sympathetic nerve activity (MSNA). Five healthy male volunteers took 3 mg of melatonin, and their plasma melatonin concentration, blood pressure, heart rate, and burst rate of MSNA were then recorded. The peak level of melatonin concentration showed a marked interindividual variation. Blood pressure was reduced significantly, while heart rate and burst rate of MSNA did not change significantly. These results indicate that melatonin has a hypotensive effect on blood pressure, and the central cardiovascular regulatory mechanism such as lowering of the baroreflex setpoint would be involved in the effect.