The role of leptin in humans remains controversial. Leptin concentrations are highly correlated with body fat stores. We tested whether or not this relation was consistent across the range of body composition encompassing the lean as well as the obese. Individuals participating in community-based comparative research in Nigeria (n = 363), Jamaica (n = 372), and the United States (Maywood, IL; n = 699) had their plasma leptin concentrations and body compositions (with bioelectrical impedance analysis) measured. All participants identified themselves as being black. Body mass index (in kg/m2) ranged from 14 to 62. Large differences in mean plasma leptin were noted across populations for both men and women in Nigeria, Jamaica, and the United States, respectively (men: 2.8, 3.9, and 6.8 microg/L; women: 10.3, 18.6, and 27.7 microg/L). An exponential function fit the relation between percentage body fat or total fat mass and leptin for men and women at each site. For women and men the exponential function with either percentage body fat or total fat mass was of the same shape, but increased by a constant in women, yielding higher leptin concentrations than in men at every level of body fat. On the basis of this broad distribution of body composition, the data suggest an exponential response of leptin to increases in body fat stores, consistent with the development of leptin resistance in individuals developing obesity. These findings likewise confirm that men and women exhibit different set points in terms of leptin production.