In rhesus monkeys, localized lesions of the anterior hypothalamus blocked the preovulatory surge of LH and the subsequent increase in serum progesterone. An injection of estradiol into these females failed to elicit an LH surge comparable in magnitude and duration to that measured in non-lesioned females. In the latter, the estrogen-induced LH surge occurred 50 to 60 hr after E2 and could be advanced 28 hr if progesterone (4 to 6 ng/ml) was given with E2. Total destruction of the medial basal hypothalamus also blocked the preovulatory LH surge; these females failed to exhibit a rise in serum LH or FSH after ovariectomy. Electrical stimulation of the medial basal hypothalamus in ovariectomized females released significant LH and FSH without visible behavioral effects. Intracranial infusion of LRF caused an increase in peripheral concentrations of LH and estrogen enhanced this response. Haloperidol and phentolamine blocked the E2-LRF induced LH response probably by acting on catecholaminergic-sensitive neurons. In monolayer cultures of male rat pituitary cells, LRF and rat hypothalamic extract increased the release of both LH and FSH into the media. Estradiol added to the system inhibited the LRF-induced secretion of LH, and 20 alpha-hydroxypregn-4-en-3-one augmented it. Testosterone enhanced the effect of LRF on FSH release; progesterone had no effect on either. TRF and dbcAMP had no effect on LH or FSH release, but they increased prolactin secretion into the media. In hypophysectomized rats, endogenous levels of LRF were increased; this increase was blocked by estrogen. These studies provide evidence of ovarian steriod influence on the hypothalamo-pituitary axis and some possible local sites of action.