The use of oral contraceptives (OC) has been associated with an increased risk of thromboembolic events in a subset of women. Factors predisposing to this problem are still not clearly defined although an increased platelet coagulant activity (CA) has been reported. This study was designed to evaluate the CA of platelets from asymptomatic current OC users compared with control subjects. The asymptomatic OC users were found to have evidence of hypercoagulability in the form of increased availability of platelet CA. These findings were present in both collagen stimulated and unstimulated platelets. In order to understand the mechanism we examined the in vitro effects of estradiol and/or progesterone on platelets. Platelets from normal males were incubated for one hour with estrogen and/or progesterone. There was no significant difference in CA of hormone treated platelets compared with control platelets from the same donor. CA was analyzed in platelets exposed to epinephrine, adenosine diphosphate, and collagen in the platelet aggregometer. Although a dose dependent effect was observed on CA of platelets exposed to the range of aggregating agents, the results show no significant difference between CA of the hormone treated and control platelets (p greater than 0.05). Likewise, platelet aggregation and release of nucleotide were not different between hormone treated and control platelets. Thus a direct effect of the hormones on platelets is an unlikely mechanism causing the increased CA seen in OC users.