Background and Methods. In postmenopausal women, the serum concentrations of endogenous sex hormones and vitamin D might influence the risk of hip and vertebral fractures. In a study of a cohort of women 65 years of age or older, we compared the serum hormone concentrations at base line in 133 women who subsequently had hip fractures and 138 women who subsequently had vertebral fractures with those in randomly selected control women from the same cohort. Women who were taking estrogen were excluded. The results were adjusted for age and weight. Results: The women with undetectable serum estradiol concentrations (<5 pg per milliliter [18 pmol per liter]) had a relative risk of 2.5 for subsequent hip fracture (95 percent confidence interval, 1.4 to 4.6) and subsequent vertebral fracture (95 percent confidence interval, 1.4 to 4.2), as compared with the women with detectable serum estradiol concentrations. Serum concentrations of sex hormone-binding globulin that were 1.0 μg per deciliter (34.7 nmol per liter) or higher were associated with a relative risk of 2.0 for hip fracture (95 percent confidence interval, 1.1 to 3.9) and 2.3 for vertebral fracture (95 percent confidence interval, 1.2 to 4.4). Women with both undetectable serum estradiol concentrations and serum sex hormone-binding globulin concentrations of 1 μg per deciliter or more had a relative risk of 6.9 for hip fracture (95 percent confidence interval, 1.5 to 32.0) and 7.9 for vertebral fracture (95 percent confidence interval, 2.2 to 28.0). For those with low serum 1,25-dihydroxyvitamin D concentrations (≤23 pg per milliliter [55 pmol per liter]), the risk of hip fracture increased by a factor of 2.1 (95 percent confidence interval, 1.2 to 3.5). Conclusions: Postmenopausal women with undetectable serum estradiol concentrations and high serum concentrations of sex hormone-binding globulin have an increased risk of hip and vertebral fracture.