The frequent use of estrogen and progestin replacement for treatment in postmenopausal women makes assessment of its effect on the coagulation system of interest. Although the amount of estrogen used to achieve the desired therapeutic effect is lower than the lowest doses in oral contraception, the age and medical condition of this population may amplify any hormone-induced risk. The common impression is that postmenopausal replacement therapy does not increase risk for thromboembolic disease, but no large epidemiologic studies of estrogen replacement have addressed that question. In this randomized prospective study, we examined the effects of varying low doses of an estrogen-progestin preparation on the titers of clotting factors in postmenopausal women. The coagulation factors selected for investigation were among those that have been reported to be significantly altered in the plasma samples of high-dose estrogen users. There were no changes in prothrombin time, factor X, fibrinogen, factor VII, or fibrinopeptide A in any of the hormone-treated groups. Mild but significant shortening of the partial thromboplastin time and elevation of factor XII titer were noted in all treatment groups. The titer of antithrombin III was reduced in the group given 20 micrograms ethinyl estradiol, but not in the groups given 5 or 10 micrograms. The clinical significance of these changes is difficult to determine in postmenopausal women receiving sex hormone replacement. However, we have not noted any thromboembolic episodes in our volunteers after a 1-year follow-up period.(ABSTRACT TRUNCATED AT 250 WORDS)