Studies were conducted using an ovariectomized rat model to determine the estrogenic and antiestrogenic activity of Trifolium pratense L. (red clover) extracts. A red clover extract, standardized to contain 15% isoflavones was administered by gavage [250, 500 and 750 mg/(kg x d)] to virgin, ovariectomized 50-d-old Sprague-Dawley rats, for 21 d in the presence and absence of 17beta-estradiol [50 microg/(kg x d)]. Estrogenic effects included an increase in uterine weight, vaginal cell cornification and mammary gland duct branching. Red clover produced a dose-dependent increase in uterine weight and differentiated vaginal cells at the two higher doses, but it did not stimulate cell proliferation in the mammary glands. Neither antiestrogenic nor additive estrogenic properties were observed in any of the tissues studied. These data suggest that red clover extract is weakly estrogenic in the ovariectomized rat model.