The purpose of this study is to clarify the significance of synthetic LH-RH (RH) as a therapeutic agent in the treatment of anovular women who fail to respond to clomiphene therapy. METHODS Fifteen women with hypofunction of the hypothalamus-pituitary system who were given the RH-test were divided into two groups according to the maximum increased level of LH shown by each. Group I consisting of 7 women who showed increased levels of over 20miu/ml received a combination of clomid+estrogen+RH(C.E.R). Blood levels of LH, FSH and estradiol were measured in each. Group II consisting of 8 women who showed maximum levels of LH below 20 miu/ml received RH intramuscularly, 100 mug per day for 20 to 30 days (referred to as RH treatment). The RH-test was performed in this group before treatment, and 1, 7 and 21 days after treatment. Blood levels of estradiol were also determined before, during and after treatment. RESULTS 1) Ovulation occurred in 5 of the 7 women in group 1 and 3 became pregnant. The LH surge was prolonged and hormonal secretion increased with administration of C.E.R.. The normal estrogen surge and gonadotropin surge occurring in the ovulatory cycle were thus produced artificially. Since administration of clomiphene alone tends to produce insufficiency of cervical mucus secretion because of its anti-estrogen effect, the addition of estrogen to the combination of C.E.R. probably increases the cervical secretion of mucus and enhances the probability of impregnation. 2) Compared to pretreatment levels, RH treatment clearly increased the pituitary secretion of LH and FSH. Even 3 weeks after RH treatment, the pituitary secretion of gonadotropin was definitely higher than before treatment. Fluctuations in blood levels of estradiol during and after treatment were not significantly different than before treatment. These observations would suggest that prolonged administration of RH enhances the gonadotropic function of the pituitary, not only in the secretion of the hormones but also in the synthesis of gonadotropin. Judging from the insignificant effect on the blood level of estradiol, it would appear that RH itself possesses the ability to produce gonadotropin.