Chronic injections of high doses of progesterone (5 mg) and low doses of estradiol benzoate (EB; 2 .mu.g) 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 h. 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 .mu.g to 6 .mu.g or 10 .mu.g offset this inhibition. High doses of progesterone (5 mg) administered simultaneously or 2-16 h prior to EB inhibited the induction of sexual behavior, but the inhibition waned when progesterone was administered 48 h 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 5 injections (.2 mg) every 4 h. The results of 2 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 CNS is not to interfere with the binding of estradiol.