Nine anovulatory patients were treated by administering pulsatile LHRH (2-20 micrograms, i.v. at 90 min intervals) for 15-58 days. These patients consisted of 4 women with hypothalamic amenorrhea, one women with oligomenorrhea, 2 women with polycystic ovarian disease (PCOD) and 2 women with hyperprolactinemic amenorrhea. Four of them were involuntarily infertile. The pulsatile LHRH therapy induced follicular maturation and ovulation, as evidenced by increased plasma estradiol levels followed by a midcycle LH surge and subsequent rise in plasma progesterone (P) levels, in 8 of the 9 patients. One patient with PCOD failed to ovulate. All of 11 treatment cycles were ovulatory in the 8 patients. A maximal P level of below 10 ng/ml was seen in 3 of the 11 induced ovulatory cycles, indicating corpus luteum insufficiency. Luteolysis occurred soon after discontinuing the pulsatile LHRH administration at the mid to late luteal phase in 3 ovulatory cycles. One of the 4 infertile women became pregnant. The results indicate that chronic pulsatile administration of LHRH is useful in inducing ovulation not only in hypothalamic amenorrhea, but also in PCOD and hyperprolactinemic amenorrhea. They also suggest that although a possible augmentation of the hypothalamic LHRH release at the preovulatory phase cannot be denied, a series of endocrine events during the human menstrual cycle may be regulated by the feedback action of the ovarian signals on the pituitary under a fixed input of the hypothalamic LHRH.