The effect of estradiol on FSH and LH secretion in 5 women with hypothalamic amenorrhea are presented. The functional capacity of the pituitary to secrete FSH and LH had been proved by testing with synthetic luteinizing hormone-releasing hormone (LH-RH) 100 mug i.m. The thyroid and adrenal functions were normal. In 3 patients estrogens were low-normal and in the other 2 extreme hypoestrogenism was found. Twelve days after the appearance of withdrawal bleeding each patient was given 10 mg estradiol benzoat (EB) i.m. In 3 patients a significant increase in the LH and a slightly smaller increase in the FSH concentration were noted, with an LH peak 60 to 84 hours after injection of EB. The first of these 3 patients became pregnant, in the second the biphasic BBT curve, urine pregnanediol excretion above 2.5 mg/24 hr and the histological finding of secretory endometrium indicated that ovulation had been successfully induced, while in the third patient, despite a satisfactory increase in the LH and FSH concentration, ovulation could not be induced. In the remaining 2 patients no increase in the LH and FSH concentrations was noted even as late as 96 hours after the injection of EB. In these women bleeding began on the 18th and 22nd day of the cycle, respectively, when histological examination revealed proliferative endometrium. The first 3 cases are classified as hypothalamic amenorrhea with dysfunction of the cyclic centre and the other 2 as hypothalamic amenorrhea with dysnfunction of the tonic centre. The effect of exogenous estrogens in patients with hypothalamic amenorrhea depends both on the functional capacity of the hypophysis and the capacity and condition of the tonic and cyclic centres in the hypothalamus.