Osteoporosis is a major health problem in postmenopausal women. Although estrogen replacement in adequate dosage can slow or even prevent bone loss, only a small percentage of postmenopausal women receive such therapy; many who do fail to comply with the prescribed regimen because of the fear of cancer and the occurrence of withdrawal bleeding, irregular bleeding, or both, and other side effects. Use of lower estrogen dosages has been suggested as a means of improving compliance and enhancing safety without compromising efficacy. Compared with standard therapy, low-dosage estrogen may minimize the increased risk of both endometrial hyperplasia and endometrial cancer. Most women find low-dosage estrogen more acceptable than higher dosages because they experience less bleeding and are more likely to become amenorrheic. Low-dosage estrogen along with sufficient calcium intake effectively maintains bone density in postmenopausal women. In the recent study of unopposed estrogen therapy described here, micronized 17 beta-estradiol in the range of 0.5 to 2.0 mg, given with dietary and supplemental calcium to ensure a minimum of 1500 mg/day, effectively maintained spinal trabecular bone density. None of the women who received the lowest dosage of 0.5 mg/day micronized 17 beta-estradiol experienced vaginal bleeding, and after 18 months the incidence of endometrial hyperplasia in this dosage group (17%) tended to be lower than those in the 1.0-mg and 2.0-mg dosage groups (29% and 22%, respectively). There was a trend toward fewer vasomotor symptoms among women who received the 0.5-mg and 1.0-mg dosages of micronized 17 beta-estradiol compared with those who received placebo. The 2.0-mg dosage group had a significantly lower incidence of vasomotor symptoms (P = 0.02) than the placebo group. Micronized 17 beta-estradiol (0.5 mg/day) with an adequate intake of dietary or supplementary calcium (1500 mg/day) is an appropriate choice for postmenopausal women in whom low-dosage estrogen therapy is indicated. This regimen, while proving efficacious in the prevention of bone loss, may be especially helpful for women who wish to minimize the bleeding that accompanies usual-dosage hormone-replacement regimens and should enhance compliance with the prescribed therapy.