Postmenopausal women receiving estrogen replacement therapy (ERT) are not as prone to inappropriate venous and arterial thrombosis as are younger women taking oral contraceptives. To establish whether menopausal status per se has any effect on the coagulation-fibrinolytic system normal premenopausal women (mean age 29 years) were compared with younger (mean age 23) and older (mean age 51) surgically menopausal women and a group of naturally postmenopausal women (mean age 53). The results show that in postmenopausal women, irrespective of age or type, the shift is away from clot formatiuon and toward clot inhibition and fibrinolysis as determined by static in vitro analysis. This was characterized by statistically significant increases in antithrombin III antigen, alpha 1-antitrypsin antigen, and plasminogen activity. These changes may help to explain in part why ERT does not appear to cause increased thrombosis in older women.