In order to elucidate the endocrinological background of patients in whom ovulation induction by pulsatile LH-RH administration resulted in failure, 16 women with hypothalamic amenorrhea were treated with 10 to 20 micrograms of LH-RH injected subcutaneously every 2 hrs. Six women did not ovulate, and 5 of them showed pituitary desensitization since the basal gonadotropin concentration gradually decreased and the response to LH-RH test (100 micrograms i.v.) became blunted by the treatment. No significant differences between the ovulated and desensitized groups were seen in basal LH, FSH, E2, PRL levels, LH/FSH ratio and response to LH-RH test performed prior to the treatment. In addition, the plasma LH-RH profile after subcutaneous injection of 10 micrograms of LH-RH was highly pulsatile in both groups. However, in the desensitized group, all were obese, showed impaired GH response to both insulin tolerance and GH-RH tests, and had episodic LH secretion with higher frequency compared to the ovulated group. These results suggest that the desensitized women had occult pituitary dysfunction and hypersecretion of endogenous LH-RH which stimulated the pituitary close to the level of desensitization. The mechanism of hypersecretion of endogenous LH-RH is discussed.