Background: Testosterone (T) associated with estrogen (E) has been used in hormsonal replacement therapy in postmenopause women and the effects of this hormonal association on the uterus are not known. Objective: To study the effect of long-term simultaneous exposure to testosterone and estrogen on the uterus of non-castrated adult female rats. Methods: Groups of ten adult noncastrated female Wistar rats were treated with non-esterified testosterone and beta estradiol (subcutaneous implants with 50 mg of each hormone) or with testosterone cipionate and estradiol valerate (weekly intramuscularly or by subcutaneous injection of respectively, 2.85 mg/kg and 0.166 mg/kg). Control groups received no treatment (10 rats) or injections of diluents (6 rats). All animals were killed six months after hormonal exposure. Results: All rats treated with T + E developed hyperplasia and hyperkeratosis of the vaginal and cervical epithelium and focal metaplasia with keratinization of the endocervical and endometrial epithelium. Ascending pelvic inflammatory disease with pyometra and tuboovarian abscesses were frequent (25% mortality until the end of the experiment). Conclusions: Testosterone associated with estrogen induced metaplasia of the genital epithelium but did not induce neoplastic lesions. The metaplasic lesions reduced the mucosal defense mechanisms enhancing ascending genital inflammatory disease. Although metaplasia of the cervical and endometrial epithelium has been observed after estrogen exposure in rats, testosterone does not appear to inhibit these estrogen effects.