There are changes in the ability to regulate energy balance and caloric intake with aging. Consequently, we investigated whether human aging modifies the levels of serum leptin, a novel hormone implicated in the regulation of energy balance. We studied 268 Caucasian men and women aged 22-85 years, and divided them into groups with mean ages of 30, 40, 50, 65, 75, 80 and 85 years. Fasting serum leptin concentrations were determined by radioimmunoassay. Subjects aged 65 or older were followed for five years after the blood sampling. There were no statistically significant differences in fasting serum leptin concentrations across different age groups in females (p = 0.090). Fasting serum leptin concentrations were also similar in different age groups in males, except that males in the 30-year age group had lower serum leptin levels than males in the 75-year age group (p = 0.042). Leptin levels were 2-3 fold higher in females than in males in each age group (p < 0.005 except p = 0.063 in the 75-year age group). Elderly women, who lived longer, had 47% higher (p < 0.05) serum leptin concentrations, and 17% higher (p < 0.001) BMI than the women who died within five years of blood sampling. Leptin levels were not statistically different in these women after adjusting for BMI. Thus, aging has no apparent effect on serum leptin levels in women or men, and the gender differences in leptin is present also in the older age groups. Higher leptin concentrations in the females who live longer may reflect a better nutritional status, and a greater adipose tissue mass rather than a primary factor for survival.