Studies both in vivo and in vitro have provided evidence that LH secretion can be altered by angiotensin II (AII) or atrial natriuretic peptide (ANP); however, the physiological significance of these endogenous neuropeptides in the control of gonadotropin release is still unclear. We studied the effects of central immunoneutralization of these neuropeptides on LH and FSH release in ovariectomized rats. Antisera directed against AII or ANP were microinjected into the third cerebral ventricle (3V) of conscious, unrestrained rats with indwelling external jugular catheters and blood samples were withdrawn immediately prior to the injections and at various intervals thereafter. Plasma LH was not altered initially but by 2 h was significantly lower in the animals injected with antiserum directed against AII (AB-AII) than in controls injected with normal rabbit serum (NRS). Values remained low for 6 h. By 24 h they had returned to levels similar to those of NRS-injected controls. On the other hand, in animals injected with antiserum against ANP (AB-ANP) plasma LH levels were significantly higher than those of controls (NRS) after a delay of 4 h. Values were still significantly elevated at 24 h. There was no difference in plasma FSH concentrations between control groups (NRS) and groups injected with either AB-AII or AB-ANP. These results indicate that endogenous AII and ANP play no role in the control of FSH release, at least in ovariectomized rats but that these neuropeptides play a role in LH release which is stimulated by AII and inhibited by ANP since the immunoneutralization decreased and increased, respectively, the plasma levels of this hormone. Thus, our results indicate that endogenous AII and ANP have physiological significance in the control of LH release.