BACKGROUND: Leptin, a hormone which is produced by adipose tissue, has been shown to inhibit food intake and increase energy expenditure. In humans, leptin levels are correlated with body fat. In addition, leptin levels decline in subjects who lose weight. Yet few data exist on whether leptin levels predict weight change, except for a recent report suggesting that low leptin levels predict weight gain in very obese middle-aged Pima Indians. METHODS: We have examined the association between baseline leptin levels and subsequent weight gain over 3.25 y in 180 non-diabetic participants in the Mexico City Diabetes Study. RESULTS: At baseline, the correlation between leptin levels and body mass index (BMI) was 0.712 in men and 0.691 in women (both P`0.001). Subjects were matched on age (AE 2 y), gender and BMI (AE 2 kgam 2 ) at baseline. Baseline BMI was 25.3 kgam 2 in men and 27.2 kgam 2 in women. Baseline leptin levels (ngaml) did not predict weight gain in either men (weight gainers: 4.3; weight stable: 5.8; and weight losers: 5.2) or women (weight gainers: 17.4; weight stable: 17.7; and weight losers: 17.4). CONCLUSIONS: We conclude that baseline leptin levels did not predict weight change in moderately obese individuals.