To clarify the role of leptin as a signal of energy status in humans, this study investigated the relationship of leptin to measures of body composition, maturity, and lifestyle factors in a lean sample of 293 male and 303 female Filipino adolescents (age 14-16 years). Participants were selected from the Cebu Longitudinal Health and Nutrition Survey, a representative birth cohort study begun in 1983. Using IOTF criteria, the prevalence of overweight (2.2%) and obesity (0.3%) were extremely low, and leptin levels were among the lowest reported in any healthy population (mean: 0.78 and 3.57 ng/dl in males and females). As expected, adiposity was the strongest predictor of leptin, with triceps skinfold explaining 40.2 and 30.6% of leptin variance in males and females. In females, subscapular skinfold was a significant predictor of leptin independent of triceps, while no anthropometric measure predicted leptin independent of triceps in males. There were few relationships between lifestyle factors and leptin independent of adiposity. In males, leptin levels varied little across most of the triceps distribution, suggesting that the leptin-adipose regulatory system is sensitive to very small changes in leptin in lean populations, at least among males. These findings add to the small but growing list of studies documenting differences in leptin biology among chronically lean populations.