The influence of serotonin on a selected dorsal hand vein can be evaluated by changes in tangential wall tension, volume, and pressure. A plethysmographic method has been used to record the changes in venous capacitance at constant pressure after IV injection of small doses of serotonin. R 41 468, a specific serotonin antagonist, has been given orally (10, 20, or 40 mg) or intravenously (2.5 or 10 mg) to healthy volunteers. A reduction or a complete blockade of activity of serotonin was observed after all doses of R 41 468. Duration and strength of the antagonism were dose-dependent. This pharmacologic in vivo model allows investigations into substances with an effect on vascular smooth muscles.