Chronic injections of high doses of progesterone (5 mg) and low doses of estradiol benzoate (EB; 2 microgram) resulted in less sexual behavior than did low doses of progesterone (.5 mg) and low doses of EB. In a typical procedure for inducing sexual behavior, EB and progesterone were given sequentially, separated by 42 hr. High levels of progesterone (2.5 and 5 mg) administered concurrently with EB inhibited the induction of sexual receptivity. Increasing the dose of EB from 2 microgram to 6 microgram or 10 microgram offset this inhibition. High doses of progesterone (5 mg) administered simultaneously or 2-16 hr prior to EB inhibited the induction of sexual behavior, but the inhibition waned when progesterone was administered 48 hr prior to EB. A single injection of progesterone (1 mg) that did not inhibit the induction of sexual behavior when administered concurrently with EB did inhibit lordosis when distributed into five injections (.2 mg) every 4 hr. The results of two experiments in which progesterone did not inhibit the uptake or retention of [3H]estradiol by brain cell nuclei suggest that the antiestrogenic action of progesterone in the central nervous system is not to interfere with the binding of estradiol.