The regulation of 3H-muscimol binding to high-affinity GABAa receptors by estradiol (E) and by progesterone (P) was studied within discrete brain regions using in vitro quantitative autoradiography. Treatment of ovariectomized and adrenalectomized female rats with E resulted in a decrease of muscimol binding only in specific estrogen-sensitive brain regions like the ventromedial nuclei (VMN) of the hypothalamus, the arcuate nucleus (ARC), the medial amygdala and the midbrain central grey (MCG). When administered alone, P had no effect. However, in estrogen-primed females, P increased muscimol binding in both VMN and MCG to levels seen in control animals. Thus, E and P exert opposite effects on the GABAa receptor within these two nuclei. As both hormones facilitate female reproductive behavior as well as the release of luteinizing hormone, present results suggest that E and P affect muscimol binding by different mechanisms.