The estrogenic actions of dietary phytoestrogens have raised concerns regarding the potential DES-like developmental effects on the female genital tract, but the growing evidence of cardioprotective benefits of dietary soybean estrogens provides the impetus to assess the effects of these compounds in adult female models of the menopause. We conducted an experiment in ovariectomized rats to determine the independent effects of dietary soybean estrogens (SBE) and the interactions of these agents with the commonly used pharmaceutical estrogen preparation (conjugated equine estrogens, CEE) in the vagina and uterus. We looked at the effects of SBE and CEE, alone and in combination, on uterine weight, body weight, vaginal cytology, uterine luminal epithelial height, and immunohistochemical staining for proliferating cell nuclear antigen (PCNA), lactoferrin (Ltf), and apoptosis. Ovariectomized rats were fed diets containing casein or soybean protein (SBE, low dose = 11.6 mg isoflavones/ 1800 cal; high dose = 117.8 mg/1800 cal), with no CEE, low dose CEE (0.313 mg/1800 cal), or high dose CEE (0.625 mg/1800 cal) added. In this study, SBE did not demonstrate estrogenic activity for uterine weight or vaginal cytology. We also found no estrogenic effects of these doses of SBE for PCNA, apoptosis, Ltf staining, or for LEH measurements. In addition, our results regarding the interactions of SBE and CEE do not show any evidence that the combination is additive in effect. On the contrary, the LEH response induced by low levels of CEE, was reduced by high levels of SBE. Furthermore, the Ltf response induced by CEE also was reduced by high levels of SBE. This suggests that high doses of SBE may antagonize the estrogen-agonist actions of low doses of CEE in the rat uterus. Our results in the ovariectomized rat model of menopause suggest that dietary soybean estrogens will not elicit a pattern of effects that simply recapitulates those of steroidal estrogens.