Some laboratories have reported sex differences in the effect of estrogen priming on neural progestin receptor concentration, whereas others find no such differences. The present studies sought to identify experimental variables which might differentially influence the measurable level of hypothalamic cytosol progestin receptors in adult male and female rats. The influence of three variables, body weight, adrenal status, and estrogen priming regimen, was evaluated. Treatment with low doses of estrogen (2 or 8 micrograms of estradiol benzoate (EB) 48 hr before sacrifice) was slightly but not significantly more effective in elevating hypothalamic progestin receptor content in age-matched females than in males despite the 40% greater body weights of males. When the same doses of EB were administered per 200 gm of body weight to animals with and without adrenal glands, both basal and estrogen-induced levels of hypothalamic progestin receptor were significantly higher in adrenalectomized/gonadectomized rats than in rats which were gonadectomized only, regardless of sex. There was no significant effect of sex or any interaction between sex, adrenal status, or estrogen priming dose. The only significant sex difference in brain progestin receptors occurred when weight-matched males and females received multiple injections of higher priming doses of estrogen (three daily injections of 10 micrograms of EB). Under these conditions, females showed up to 2-fold higher levels of hypothalamic progestin receptors than males, regardless of adrenal status. These data suggest that sex differences may exist in the neural progestin receptor systems of male and female rats, but the relationship of these differences to sex differences in neuroendocrine function or behavior is not clear.