The histologic pattern of the endometrium was studied in 38 patients, 19 to 44 years old, with primary hypoestrogenic amenorrhea treated by estrogen replacement therapy. At the time of endometrial biopsy 3 patients were receiving estrogens only and 35 patients were taking 1 of the following cyclic estrogen-progestogen combinations: 1) conjugated estrogens, 1.25 or 2.5 mg per day, combined with medroxyprogesterone, 5 or 10 mg for the last 5 to 10 days; 2) ethinyl estradiol, 50 microgram per day, combined with medroxyprogesterone, 5 mg per day for the last 5 days; or 3) mestranol, 40 microgram per day, in combination with norethindrone, 0.5 mg for the last 7 days. Evidence of endometrial hyperplasia was found in 3 patients. Two of them were taking unopposed estrogens and developed cystic hyperplasia; the other patient, treated with norethindrone in addition to mestranol, disclosed focal cystic glandular hyperplasia. This study and the review of the available data reported in the literature on the endometrial response to estrogen therapy in patients with gonadal dysgenesis stress the importance of appropriate estrogen and progestogen dosage to avoid the hazards of abnormal endometrial pattern in young patients receiving estrogen replacement therapy.