NPY acts both at the hypothalamus and the anterior pituitary gland to modulate reproductive hormone secretion. Within the hypothalamus, NPY stimulates LHRH secretion in the presence of physiological levels of estrogen and suppresses pulsatile LHRH release following ovariectomy. Intracerebroventricular injection of NPY antiserum blocks or delays the LH surge in steroid-primed ovariectomized rats, thereby adding support for a physiological role of NPY in the neuroendocrine events preceding ovulation. Blockade of alpha 2 adrenergic receptors decreases NPY-stimulated LH release in steroid-primed rats implying a potential noradrenergic mediation of NPY activity. Physiological levels of progesterone do not augment, and may actually suppress NPY-induced LHRH secretion in vitro from median eminences obtained from estrogen-primed ovariectomized rats. The physiological role of progesterone, if any, in modulating NPY effects on LHRH release remains to be determined. Little, if anything, is known about the NPY receptor in the median eminence or the intracellular mechanisms which transduce the NPY signal into activation of LHRH release in estrogen-treated ovariectomized rats although translocation of intracellular calcium is required. Equally puzzling is the mechanism of desensitization of the LHRH-releasing mechanisms of the median eminence of ovariectomized rats or the specific site of NPY suppression of pulsatile LHRH secretion. NPY is released into the hypothalamo-hypophysial portal circulation and this appears correlated with LHRH secretion before the LH surge. NPY affects LH and FSH release from anterior pituitary cells in vitro and enhances LHRH-induced LH secretion. Taken together, the studies described above suggest an important physiological role for NPY as a modulator of neuroendocrine activity which culminates in the preovulatory surge of LH.