Both serum leptin and bone mineral density are positively corre- lated with body fat, generating the hypothesis that leptin may be a systemic and/or local regulator of bone mass. We investigated 214 healthy, nonobese Australian women aged 20 -91 yr. Bone mineral content, projected bone area, and body fat mass were measured by dual energy x-ray absorptiometry and fasting serum leptin levels by RIA. Associations between bone mineral content (adjusted for age, body weight, body fat mass, and bone area) and the natural logarithm of serum leptin concentrations were analyzed by multiple regression techniques. There was a significant positive association at the lateral spine, two proximal femur sites (Ward's triangle and trochanter), and whole body (partial r2 5 0.019 to 0.036; all P , 0.05). Similar trends were observed at the femoral neck and posterior-anterior-spine. With bone mineral density the dependent variable (adjusted for age, body weight, and body fat mass), the association with the natural logarithm of leptin remained significant at the lateral spine (partial r2 5 0.030; P 5 0.011), was of borderline significance at the proximal femur sites (partial r2 5 0.012 to 0.017; P 5 0.058 to 0.120), and was not signif- icant at the other sites. Our results demonstrate an association be- tween serum leptin levels and bone mass consistent with the hypoth- esis that circulating leptin may play a role in regulating bone mass. (J Clin Endocrinol Metab 86: 1884 -1887, 2001)