The effects of medroxyprogesterone acetate (MPA) on the mechanism of coagulation in postmenopausal patients were studied and compared with those of tamoxifen by a retrospective analysis. The coagulation test parameters tested included platelet count, bleeding time, clotting time, prothrombin time, activated partial thromboplastin time, and the levels of fibrinogen, fibrin degradation products, factor II, factor V, plasminogen, alpha 2-plasmin inhibitor (alpha 2-PI) and alpha 2-plasmin inhibitor-plasmin complex (alpha 2-PI-P). A shortened APTT was noted and the levels of factors II, V, alpha 2-PI and alpha 2-PI-P were also out of the normal range during treatment in the MPA-treated group. However, these abnormal parameters recovered to within the normal range from 6 months or more after the commencement of treatment without any termination of drug administration. The patients were all asymptomatic. In contrast, a slight prolongation of bleeding time which persisted for more than 6 months was observed in the patients treated with tamoxifen. These data suggest that MPA causes a hypercoagulable state and that any change must be carefully monitored during treatment with either MPA or tamoxifen.