The objective of this study was to determine if kappa-opioid receptors present in the medial preoptic area (MPOA) and medial basal hypothalamus (MBH) are involved in opioid peptide suppression of LH secretion during midpregnancy (day 13-16) in the rat. Nor-binaltorphimine (nor-BNI), a selective antagonist of brain kappa-opioid receptors, was applied directly to the MPOA or MBH for 3.5 h by means of push-pull perfusion. Nor-BNI perfusion in the MBH produced a dose-dependent increase in LH pulse frequency as well as increases in blood LH level. The effect on amplitude could not be determined, since too few pulses occurred in cerebrospinal fluid-treated control rats. Nor-BNI perfusion in the MPOA also increased LH pulse frequency. Moreover, in the majority (62%) of rats perfused with nor-BNI in the MPOA, the final 1.5 h of perfusion were unexpectedly characterized by an increase in LH that was of greater magnitude and more prolonged than an LH pulse and produced an elevation in blood LH levels. This delayed LH response did not occur in any rat perfused in the MBH. Perfusion with nor-BNI in the diagonal band of Broca had no significant effect on LH secretion. The LH responses observed during nor-BNI perfusion in the MPOA or MBH were not due to spread to the third ventricle and subsequent diffusion via the cerebrospinal fluid to another brain site, since perfusion with nor-BNI in an area of the ventral thalamus close to the third ventricle had no effect on LH release. These results provide support for the involvement of kappa-opioid receptor-mediated mechanisms in both the MPOA and MBH in the suppression of LH secretion during midgestation in the rat.