Estrogen appears to play an important role in determining bone mineral density in men, but it remains unclear whether estrogen primarily determines peak bone mass or also affects bone loss in elderly men. Thus, we assessed longitudinal rates of change in bone mineral density in young (22-39 yr; n = 88) vs. elderly (60-90 yr; n = 130) men and related these to circulating total and bioavailable estrogen and testosterone levels. In young men bone mineral density increased significantly over 4 yr at the mid-radius and ulna and at the total hip (by 0.32-0.43%/yr), whereas it decreased in the elderly men at the forearm sites (by 0.49-0.66%/yr), but did not change at the total hip. The rate of increase in bone mineral density at the forearm sites in the young men was significantly correlated to serum total and bioavailable estradiol and estrone levels (r = 0.22-0.35), but not with total or bioavailable testosterone levels. In the elderly men the rates of bone loss at the forearm sites were most closely associated with serum bioavailable estradiol levels (r = 0.29-0.33) rather than bioavailable testosterone levels. Moreover, elderly men with bioavailable estradiol levels below the median [40 pmol/liter (11 pg/ml)] had significantly higher rates of bone loss and levels of bone resorption markers than men with bioavailable estradiol levels above 40 pmol/liter. These data thus indicate that estrogen plays a key role both in the acquisition of peak bone mass in young men and in bone loss in elderly men. Moreover, our findings suggest that age-related decreases in bioavailable estradiol levels to below 40 pmol/liter may well be the major cause of bone loss in elderly men. This subset of men is perhaps most likely to benefit from preventive therapy.