The acute administration of 0.015-1.5 nmol ovine corticotropin-releasing factor (CRF) into the lateral ventricle of gonadectomized (or gonadectomized/adrenalectomized) female rats caused a rapid and prolonged dose-related inhibition of LH (but not FSH) secretion. By contrast, the acute peripheral injection of up to 15 nmol CRF was without effect in the same animal preparations. In cycling intact female rats, injection of 1.5 nmol CRF into the brain or of 75 nmol CRF sc inhibited ovulation and blocked the proestrous LH surge in about 50% of the animals. Lower doses of peripherally administered CRF were ineffective. Finally, CRF injected daily sc (15 nmol/day) to female rats during the first 12 days after mating caused a 40% disruption of pregnancy. These results indicate that CRF will lower plasma LH levels and can exert this effect in the absence of circulating steroids of either adrenal or gonadal origin. CRF inhibition of LH secretion, which we have previously reported to be absent in vitro, was unaltered by the opiate receptor antagonist naltrexone or by the ganglionic blocker chlorisondamine. Furthermore, blockade of CRF-induced beta-endorphin or ACTH release into the general circulation by dexamethasone did not interfere with the inhibitory effect of CRF on LH secretion. Such observations suggest that CRF exerts deleterious actions on reproductive functions through brain sites of action which, at least under the experimental mental design used, do not appear to directly involve opiate or peripheral catecholaminergic pathways.