The competitive effects between trans- and cis-clomiphene and estradiol benzoate (EB) were evaluated as to their ability to induce sexual behavior in ovariectomized female rats. Study groups always contained 6–12 animals per group. One group received 2.5 mg trans- while the other received 5 mg of the cis-/trans-ra.cemic mixture (Clomid®) for 10 days. All groups received 500 μg progesterone (P) on day 11. Behavioral tests performed on the afternoons of days 5, 10 and 11 were scored for lordosis response. 2.5 mg of trans- significantly increased (p < 0.01) the lordosis response on all test days when compared to the 5 mg cis-/trans- group. Thus, cisinterferes with the ability of trans- to induce sexual behavior. The effects of cis- and transgiven concomitantly with varying doses of EB were also tested. Controls received 0.1 μg, 0.25 μg or 1.0 μg EB for three days. Treatment groups received the same doses of EB and 100 μg of cisor 100 μg of trans-. All animals received 500 μg P on day 4. In this test regime cis- did not alter the lordosis response whereas trans- significantly increased (p < 0.01) lordosis to 0.1 μg EB suggesting that trans- and EB act synergistically. In order to study the effects of clomiphene pre-treatment one group received 1 mg cis- on days 1–4 and EB 0.25 μg on days 2–4 while the other received only the EB on days 2–4. All animals received 0.5 mg of progesterone on the morning of day 5 and a behavioral test later that afternoon. Pre-treatment with cis- significantly depressed (p < 0.01) sexual behavior, suggesting that it inhibited the action of EB. In conclusion: trans- is effective in inducing sexual behavior in the absence of EB. Trans- and EB, given together in low doses, act synergistically to induce sexual behavior substantiating the point that trans- has estrogenic activity. On the other hand, cis- will not induce sexual behavior and will compete with trans- causing a diminution in estrous behavior. Cis- does not act synergistically with EB, and instead will block EB-induced sexual behavior if given first. The actions of trans- and cis- clomiphene are probably due to their estrogenic and anti-estrogenic activity, respectively. (Endocrinology93: 681, 1973)