We conducted a controlled study of the effects of oral estrogen therapy in postmenopausal women with established postmenopausal osteoporosis. Bone mass was measured in the lumbar vertebrae and hip using dual photon absorptiometry. Both estrogen-treated women and the control group received calcium supplements to bring total intake to approximately 1500 mg/day. For those women with an intact uterus in the estrogen wing of the study, a progestin was added to the therapy for 12-14 days each calendar month. The number of years from menopause was 14.6 +/- 0.9 in the estrogen-treated group and 13.7 +/- 1.1 in the calcium-treated group. Estrogen treatment was associated with increased vertebral bone mass by dual photon absorptiometry during the 2 years of the study (+10.6%; P less than .01). There was also an increase in bone density at the femoral neck (+5.5%; P less than .1), but the difference from the initial value was not statistically significant. The group given calcium alone lost bone at both sites, although the loss was not statistically significant at either site. The response to estrogen was greatest in those who were furthest from menopause (r = 0.38, P less than .05) and consequently among those who had the lowest bone mass (r = -0.34, P less than .05). Estrogen therapy appears to be an effective therapy for patients with established osteoporosis. Intervention is associated with a significant increase in bone mass compatible with reduced skeletal turnover and activation frequency.