Previous research has demonstrated that the circadian rhythm of melatonin negatively correlates with that of the sensitivity of platelet serotonin uptake sites. Moreover, serotonin has been found to be a competitive inhibitor of melatonin binding to platelets. The goal of the present study was to investigate whether melatonin directly affects platelet serotonin transport. Blood samples from 12 healthy subjects were assayed for both serotonin transport into platelets. Active transport of serotonin (at a concentration of 10(-6) M) into blood platelets was measured in the presence of melatonin at physiological concentrations (10(-12) M to 2 x 10(-9) M) and high nonphysiological concentrations (2 x 10(-8) M to 2 x 10(-3) M). Melatonin inhibited serotonin uptake by blood platelets at the high concentrations only ( > 10(-5) M with IC50 value of 1.1 x 10(-3) M) and had no effect at physiological concentrations.