Leptin, the product of the obese (ob) gene, is a regulator of food intake and energy metabolism. Immunoreactive leptin was detected recently in breast milk and it has been hypothesized that leptin may be absorbed and may contribute to differences in body composition between breast-fed and formula-fed infants.The objective was to evaluate whether diet, adiposity, or sex affect plasma leptin in breast-fed and formula-fed infants.Venous blood samples were drawn from healthy, exclusively breast-fed or formula-fed Swedish infants at 1, 4, and 6 mo of age (n = 193) and from 12-mo-old Finnish infants (n = 79). Anthropometric measurements were made and plasma samples were analyzed for leptin, insulin, and glucose.There were no significant differences in plasma leptin between formula-fed and breast-fed infants at 1 and 4 mo of age, whereas formula-fed infants had significantly higher ( approximately 5%) leptin concentrations at 6 mo of age. Similar results were observed after correction for BMI. Plasma leptin was 15-25% higher in female than in male infants at 1, 4, and 12 mo of age (P < 0.05), also after correction for BMI. When all infants were analyzed together, a positive correlation (r = 0.34, P < 0.0001) was found between plasma leptin and BMI. Very low leptin concentrations were found in breast milk after centrifugation and the high concentrations reported previously were likely due to interference in the assay by milk fat.Plasma leptin concentrations are not higher in breast-fed than in formula-fed infants; however, sex and adiposity affect leptin concentrations even at this early age.