The role of exogenous estrogens in the pathogenesis of endometrial hyperplasia and carcinoma was studied. Endometrial biopsies were obtained from 46 hypogonadal patients (44 with gonadal dysgenesis; 2 panhypopituitary) who were receiving estrogen-progestogen therapy. Endometrial abnormalities occurred only in patients receiving a total lifetime conjugated estrogen dose of .gtoreq. 2500 mg and who had received estrogen treatment for a period longer than 4.2 yr. The biopsy outcome was significantly related (P < 0.01) to the estrogen dose at time of biopsy and to the total lifetime dose (P < 0.05). The progestational drugs administered did not protect against development of endometrial abnormalities. None of the abnormal endometrial patterns were associated with abnormal vaginal bleeding.