Uterine glycogen accumulation was studied in ovariectomized rats treated with all combinations of clomiphene citrate (0.25 mg/kg) estradiol (1.0 micron g) and progesterone (5.0 mg). The rats were given three consecutive daily dosages and killed 24 hours after the final dosage. Based on biochemical data, either estradiol or clomiphene increased uterine glycogen concentration and total glycogen, but progesterone did not. Progesterone significantly suppressed both the estradiol and clomiphene-induced glycogen increases. Based on the histochemical results, progesterone also suppressed the estradiol and clomiphene-induced glycogen responses, but the tissue affected differed. Clomiphene markedly increased luminal epithelial glycogen whereas estradiol induced primarily myometrial glycogenesis. Progesterone completely suppressed the clomiphene-induced epithelial effect and partially suppressed the estradiol-induced myometrial effect. Clomiphene also suppressed the estradiol-induced myometrial response. The results indicate that progesterone does have a significant interaction with clomiphene in the control of uterine morphology and biochemistry. The results also stress the importance of correlated histochemical and biochemical studies in the study of clomiphene-induced uterine glycognesis.