How estrogen therapy influences bone metabolism in postmenopausal women has previously been studied using several approaches, including bone densitometry, measurement of biochemical markers of bone turnover, and histomorphometry. Taken together, these investigations suggest that conventional doses of estrogen protect from bone loss predominantly through suppression of bone resorption, with little evidence to suggest that a stimulatory action on osteoblasts is also involved. In contrast, studies of patients treated with estradiol implants suggest that, following prolonged exposure to relatively high estrogen levels, an additional stimulatory effect on osteoblast function is observed. The suggestion that estrogen stimulates osteoblast activity in postmenopausal women under certain circumstances is consistent with other evidence that estrogen is an important physiological regulator of osteoblast activity. Furthermore, these findings raise the possibility that it may be useful to develop strategies for treating postmenopausal osteoporosis that aim to reproduce the stimulatory action of relatively high estrogen levels on bone formation in postmenopausal women.