The effect of serotonin on vascular fragility, visible as petechiae, was examined in antiplatelet serum-induced thrombocy topenic hamsters. Serotonin was administered intravenously or intraperitoneally, and following a single injection of 0.5 mg/l00 g body weight, a temporary inhibition of petechial formation for approximately 1 h was observed. Repeated serotonin injections maintained animals free of petechiae for the 4-hour period of administration. Plasma levels of serotonin and the effect of serotonin on cutaneous perfusion were not significant factors in the observed inhibition of petechiae. The data suggest that in normal animals platelet serotonin may contribute more to maintaining microvascular structural integrity than platelet adhesion.