To test the hypotheses that baseline concentrations of sex steroids, sex hormone binding globulin (SHBG), and calciotropic hormones predict rates of bone loss in elderly women, sera were stored at - 190°C, and calcaneal bone mineral density (BMD) was measured in 9704 community-dwelling white women aged 65 and over (1986-1988). Hip BMD was measured 2 years later (1990). Repeat measurements of calcaneal and hip BMD were obtained in 1993-1994, after 5.7 and 3.5 years of follow-up, respectively. In 1994, sera were assayed for circulating hormone levels in random subcohorts of 231 and 218 women who did not report current use of hormone replacement therapy at baseline. Lower levels of endogenous estrogens and higher SHBG concentrations were associated with more rapid subsequent bone loss from both the calcaneus and hip. After adjusting for age and weight, women with high SHBG levels (highest quartile ≤ 2.3 μg/dl) experienced an average of 2.2% (95% confidence interval = 1.6%, 2.9%) calcaneal bone loss per year compared with 1.2% (0.7%, 1.2%) among women with low SHBG concentrations (lowest quartile < 1.1 μg/dl; p < 0.01). This association was independent of concentrations of other sex hormones. Women with estradiol levels ≤ 10 pg/ml averaged only 0.1% (-0.7%, 0.5%) annual hip bone loss while women with levels below 5 pg/ml averaged 0.8% (0.3, 1.2) hip bone loss per year. Lower 25-hydroxyvitamin D levels were associated with increased hip but not calcaneal bone loss. Levels of parathyroid hormone, 1,25-dihydroxyvitamin D, and calcium were not significantly associated with bone loss from the calcaneus or hip.