The effects of prenylamine, verapamil, propranolol, INPEA, and pindolol on the uptake of serotonin by human platelets were investigatedin vitro andin vivo. Serotonin uptakein vitro was diminished by these drugs. Their order of potency, according to IC 50 values estimated from the dose response curves was: propranolol > prenylamine > verapamil > INPEA > pindolol. The inhibitory activity of these drugsin vivo was also studied by measuring serotonin uptake by platelets isolated 90 min after oral administration to healthy volunteers of 10 µmoles of propranolol, INPEA and prenylamine, all approximately 3 mg/kg; verapamil, approximately 5 mg/kg; and 2 µmoles/kg (0.5 mg/kg) of pindolol. In agreement with the degree of inhibition observedin vitro, propranolol was more effective than verapamil and INPEA, and, as predicted from thein vitro experiments, pindolol showed no measurable membrane activity. Prenylamine, an effective inhibitor of serotonin uptake by human plateletsin vitro, was activein vivo only after repeated oral doses of 10 µmoles/kg. It is concluded that measurement of the uptake of serotonin by human platelets is a sensitive method for investigating non-specific effects of drugs on membrane functionsin vivo as well asin vitro.