OBJECTIVE: To evaluate the effect of hormone replacement therapy on platelet function in postmenopausal women. METHODS: In 51 postmenopausal women, platelet aggregation and adenosine triphosphate (ATP) release were studied before and after estrogen and progestogen treatment and compared with that in untreated patients. An incubation study evaluated platelet function after incubation with estrogen and progestogen. RESULTS: Significant decreases in adrenaline-induced platelet aggregation (P < .01) and ATP release (P < .02) were observed 3 months after initiation of estrogen replacement. Patients receiving replacement regimens consisting of estrogen opposed by progestogen or progestogen alone showed nonsignificant changes in platelet aggregation and release. The most pronounced decrease in platelet function in the incubation assay was detected after incubation with estrogen plus progestogen. Results were similar in the spontaneous- and surgical-menopause patients. CONCLUSION: Estrogen replacement therapy may inhibit the atherosclerotic process by suppressing platelet function.