Although sexual behavior during the rat estrous cycle is dependent on estradiol and progesterone, under some conditions, it can be induced by treatment with estradiol alone. Either chronic exposure to estradiol (estrogen-induced sexual behavior) or an acute large injection of estradiol in estradiol-primed rats (estrogen-facilitated sexual behavior) is capable of inducing sexual receptivity. It has been suggested that this progesterone-independent sexual behavior is referable to estradiol interaction with neural progestin receptors. A series of experiments was performed to investigate the possible dependence of estrogen-induced and estrogen-facilitated sexual behavior on neural progestin receptors. In the first series of experiments, the progesterone antagonist, RU 486, which inhibits progesterone-facilitated sexual behavior by interaction with progestin receptors, was injected into rats that were sexually receptive as a result of continuous exposure to estradiol. In the second series of experiments, RU 486 was injected prior to or following an acute large dose of estradiol (1 mg) in an attempt to block estradiol-facilitated lordosis. Although RU 486 was effective in inhibiting progesterone-facilitated sexual behavior in an identical procedure, in no case was RU 486 effective in inhibiting sexual behavior induced by estradiol alone. These findings, together with the fact that rats in which sexual behavior is facilitated by estradiol show much lower levels of soliciting behaviors than progesterone-facilitated rats, suggest that estradiol does not facilitate sexual behavior through the same mechanism as progesterone.