Although estradiol (E2) may have some beneficial effects as a treatment for menopause symptoms, E2 also has trophic effects that can increase vulnerability to some cancers, such as breast cancer. In the present study, a model to investigate the concomitant behavioral and proliferative effects of E2 was developed. First, the effects of different duration of chronic E2 exposure (2 vs 6 months), or no such exposure, on proliferation (tumor incidence and weight, uterine weight) in adult, ovariectomized (OVX) rats was determined. Second, the effects of different dosages of E2 (0.03 or 0.09 mg/kg) compared to vehicle only on sexual behavior, and measures of proliferation of adult OVX rats treated with a chemical carcinogen (DMBA; 1.25, 12.50, or 25.00 mg), or inert vehicle, were investigated. Vehicle or E2 was administered subcutaneously (SC) to OVX rats once per week for 14 weeks. Six months of continuous E2 exposure increased tumor incidence, tumor weight, and uterine weight, compared to 2 months of E2 or no E2 exposure. Rats administered DMBA had increased incidence, number, and size of tumors compared to vehicle treatment, and this effect appeared to be augmented by E2. Compared to vehicle, E2 increased lordosis and uterine weight. Thus, E2 may have the unfavorable effect of increasing proliferation when administered in chronic situations. Studies investigating the action of E2 for these effects are ongoing.