OBJECTIVE: To evaluate the influence of overweight, waist circumference, age, gender, and insulin resistance as risk factors for hyperleptinemia. RESEARCH METHODS AND PROCEDURES: A cross-sectional study was carried out in a population of 197 subjects: 59 men (21 aged < 60 years and 38 aged > or =60 years) and 138 women (37 aged < 60 years and 101 aged > or =60 years). The groups were stratified by overweight and normal weight. After a 12-hour fasting period, we measured serum leptin and insulin levels with radioimmunoassay methods. We also measured serum glucose and lipid profile. The data were analyzed by means of comparative tests. A variance-stabilizing transformation (natural logarithmic) was used to meet multiple linear regression, analysis of covariance, and logistic regression models. RESULTS: The leptin serum levels were higher and statistically significant in young and older women than they were in men. We observed an interaction between gender and body mass index to explain the difference in leptin levels (p < 0.0001). Our study demonstrated an inverse relationship between leptin with age and high-density lipoprotein cholesterol. In logistic regression analysis, the overweight x gender interaction and waist circumference have a statistically significant influence as independent variables on hyperleptinemia (overweight x gender odds ratio = 6.81; 95% confidence interval, 1.10 to 46.86; p < 0.05 and waist circumference odds ratio = 4.34; 95% confidence interval, 1.47 to 12.83; p = 0.001). DISCUSSION: Women who were overweight or had a higher waist circumference (women > or = 88 cm and men > or = 102 cm) have a significantly higher risk of having hyperleptinemia. The increase in age as an isolated variable is not a risk factor for hyperleptinemia.