The major concern with the use of unopposed estrogen is its neoplastic effect on the endometrium. Progestins used to oppose the estrogen may be associated with vaginal bleeding and reversal of estrogen's protective changes in serum lipoprotein concentrations. A study was performed in which all postmenopausal women received conjugated equine estrogen for days 1–28; with group I receiving 2.5 mg medroxyprogesterone acetate for days 1–28, group II receiving 5 mg medroxyprogesterone acetate for days 1–28, and group III receiving 5 mg medroxyprogesterone acetate for days 17–28. Pre- and postdrug evaluations of the endometrium revealed atrophic changes after therapy with continuous combined estrogen-progestin. Pre- and poststudy evaluation of serum lipoprotein concentrations demonstrated significant declines in cholesterol and low-density lipoprotein cholesterol within groups I and III, and no change in group II. All patients kept a weekly diary recording any vaginal bleeding or change in vasomotor symptoms. The results suggest that a continuous regimen of 0.625 mg conjugated equine estrogen with 2.5 mg medroxyprogesterone acetate is beneficial as a primary hormonal replacement therapy for the postmenopausal patient.