Fourteen patients with hypogonadotrophic eunuchoidism (HE), 10 males and 4 females, received luteinizing hormone-releasing hormone (LH-RH) as 4-h intravenous infusions of 0.2 \g=m\g/min or as subcutaneous (sc) injections of 200 \g=m\g.Repeated LH-RH administration over 4 days (200 \g=m\g sc daily) was undertaken in 8 patients. Eight of the 10 males and all 4 of the females were found to have definite elevations of luteinizing hormone (LH) and follicle stimulating hormone (FSH) following their first exposure to exogenous LH-RH. The patients included 2 males and 1 female with variant forms of HE, all of whom showed responses of both gonadotrophins. When the first exposure of HE patients to exogenous LH-RH was as a 4-h infusion, the biphasic pattern of LH increase characteristic of normal adults was not found. Instead, a monophasic and qualitatively small LH increase occurred, similar to that found in pre-pubertal children and in anorexia nervosa. sc/day) produced a normal biphasic LH increase. These results imply that maintenance of the two pools of pituitary LH demonstrable in normal adults depends on adequate production of endogenous LH-RH. Increases in FSH following the initial exposure to LH-RH were generally as great or greater than those of normal adults in spite of the fact that LH responses tended to be smaller than those of adults. Four days of LH-RH administration (200 sc daily) did not lead to consistent increases in gonadotrophin responsiveness. Increases of testosterone or oestradiol production could not be demonstrated, even with 4 to 5 days of LH-RH administration. Exogenous sex hormone therapy markedly inhibited gonadotrophin responsiveness to LH-RH.