Leptin may play an important role in the regulation of body weight by influencing energy intake and expenditure. Differences in body composition, resting energy expenditure (REE), and physical activity between African-American and Caucasian women could be reflective of racial differences in plasma leptin concentrations. Thus, we examined racial differences in leptin levels and the relationships of leptin to body composition and resting metabolism in obese postmenopausal African-American (n = 28) and Caucasian (n = 29) women matched for level of body fat. African-American and Caucasian women were similar in age (64.1 +/- 1.3 vs. 63.2 +/- 1.0 yr), body weight (84.7 +/- 3.3 vs. 80.4 +/- 1.3 kg), adipose tissue mass (39.7 +/- 2.8 vs. 38.0 +/- 1.0 kg), waist to hip ratio (0.81 +/- 0.02 vs. 0.81 +/- 0.01), and maximal aerobic capacity (1.5 +/- 0.05 vs. 1.6 +/- 0.05 L/min). African-American women had greater lean tissue mass than Caucasian women (41.8 +/- 1.1 vs. 39.3 +/- 0.6 kg; P = 0.05). The leptin concentration was 20% lower in African-American than Caucasian women (36.0 +/- 4.8 vs. 45.8 +/- 3.5; P < 0.05), whereas REE values were similar. Leptin correlated strongly with percent body fat in African-American (r = 0.71; P < 0.0001) and Caucasian women (r = 0.61; P < 0.001) and with REE in African-American (r = 0.58; P < 0.001), but not Caucasian, women (r = 0.08). These findings suggest racial differences in plasma leptin levels and in leptin's role in the regulation of REE, which may play a role in the greater incidence of obesity in the African-American compared to the Caucasian population.