Eight patients who required prolonged estrogen replacement therapy were implanted with two 25-mg pellets of estradiol-17β and were followed with serial measurements of serum estradiol, estrone, follicle stimulating hormone, luteinizing hormone, and maturation index of the vaginal smears. There was a significant increase in estrogen levels within 24 hours after pellet implantation, and this level was maintained in physiologic premenopausal range during the rest of the period of followup. Gonadotropins were suppressed to a greater degree in gonadal dysgenesis patients as compared to postmenopausal patients. There was rapid relief of vasomotor symptoms within 4-10 days even though the gonadotropin levels were high. Implantation of 50 mg of estradiol pellets and periodic withdrawal bleeding with a progestational agent seems to he an effective method of long-term replacement therapy.