The effects of the antiestrogens tamoxifen and keoxifene on the bone density of intact and ovariectomized female rats were determined after 4 months of therapy. The antiestrogens did not cause a decrease in bone density in intact animals, although uterine wet weight did decrease. Ovariectomy caused an increase in body weight (25%) and a significant decrease in femur density (P less than 0.01). Antiestrogens did not further decrease the bone density of ovariectomized rats but rather helped to maintain bone density. Antiestrogens as well as estrogen (oral estradiol benzoate 25 micrograms daily) helped to maintain bone density in the range observed for the intact rats, but inhibited estrogen stimulation of uterine weight. These contrasting pharmacological actions of antiestrogens suggest that patients receiving long-term adjuvant tamoxifen therapy for breast cancer should be evaluated to determine whether tamoxifen can retard the development of osteoporosis.