The induction of progestin receptors by estradiol in the mediobasal hypothalamus (MBH) has been correlated with progesterone facilitation of sexual receptivity in female guinea pigs. We used an immunocytochemical technique to visualize the induction of progestin receptors by estradiol in a population of neurons correlated with estradiol-induced responsiveness to progesterone. Progestin receptor-immunoreactivity (PR-IR) and responsiveness to progesterone-facilitation of sexual behavior were induced by intracranial implantation of small bilateral cannulae (28- or 33-gauge) containing 1 or 10% estradiol diluted with cholesterol. In the first experiment, 28-gauge cannulae containing estradiol were effective only when implanted in the rostral part of the MBH. In the second experiment in which 33-gauge cannulae were used, behavioral responsiveness to progesterone was induced only when the cannulae were localized bilaterally in the rostro-ventral part of the ventrolateral hypothalamus (VLH). The presence of estradiol-induced PR-IR within the rostro-ventral VLH was correlated with the ability of progesterone to facilitate sexual behavior. These data suggest that neurons containing estrogen-induced progestin receptors specifically within the rostro-ventral VLH are involved in progesterone facilitation of sexual receptivity in estradiol-primed guinea pigs.