To assess whether activation of platelets by catecholamines contributes to the increase in platelet aggregation associated with either the assumption of upright posture or exercise, we studied the effect of oral yohimbine on these phenomena. Whole blood platelet aggregation and plasma catecholamine levels were measured before and after standing and at peak exercise in untreated normal subjects and after oral yohimbine. Neurochemical indexes indicated systemic ⍺₂-receptor blockade by yohimbine. Yohimbine reduced the orthostatic increase in platelet aggregation response by 63 ± 11%, but exercise-induced increase in aggregation was unaffected. Thus, ⍺₂-adrenergic blockade attenuates the orthostatic increase in platelet aggregation. Agents designed to inhibit the morning surge in catecholamine levels or block platelet ⍺₂ adrenoceptors may reduce the risk of thrombotic vascular events in atherosclerosis.