A series of experiments assessed whether the ability of the antiestrogen CI-628 to inhibit estrogen-stimulated lordosis in adult ovariectomized rats depends upon its interference with the synergistic effects of estrogen with progesterone. In Experiment 1, the effect of CI-628 was contrasted in rats brought into estrus by a single subcutaneous injection of estradiol benzoate (EB) combined with an injection of progesterone (P) 42 hr later versus four daily injections of EB (without any P). CI-628 was given at the time of EB injection(s). CI-628 substantially and equally effectively antagonized lordotic responding in both conditions. In the absence of CI-628, rats receiving progesterone had significantly higher lordosis scores than the 4-day EB control animals. In Experiment 2, rats receiving CI-628 on only the first 2 of 4 days of EB injections had significantly decreased lordosis scores unless P was also given on the day of testing. This suggested that the EB from the latter injections was not acting as a progestin "mimic." In Experiment 3, lordotic responding stimulated by EB (without P) was inhibited by CI-628 in rats that were both ovariectomized and adrenalectomized. This suggested that adrenal progestins were not involved in the ability of CI-628 to inhibit lordosis. Taken together, the results suggest that the mechanism of action of CI-628 for the inhibition of lordosis does not depend upon its ability to antagonize an estrogen-induced increase in neural progestin receptors. Implications of this for estrogen-mediated behaviors, for which CI-628 has little or no antagonistic effects, are discussed.