Objective: Leptin, the product of the ob gene, is a hormone secreted by adipocytes. This study aimed to measure serum concentrations of leptin in normal - weight subjects (body mass index between 18 and 25) and obese subjects (body mass index greater than or equal to 30). It is designed to support an important role for leptin in human metabolism and obesity, Methods: One hundred lean subjects aged (33.16 +/- 12.47) years and 193 obese subjects aged (38.6 +/- 13.5) years, and 73 obese non-insulin dependent diabetes aged (51.9 +/- 9.6) years were included in the study, where as obesity was defined as a body mass index greater than or equal to 30 serum leptin concentrations were measured using a newly developed radioimmunoassay. Results: The mean +/- SD serum leptin concentrations were 25.99 +/- 15.4 ng per milliliter in the obese subjects and 5.84 +/- 5.27 ng per milliliter in the normal weight subjects (P less than or equal to 0.001). Serum leptin concentrations in specimens from lean and obese adults correlated directly with body mass index (body mass index; Kg/m(2)) (r = 0.74, P less than or equal to 0.001). Correlations were significantly improved by separating results by gender (men r = 0.85, women r = 0.72; P less than or equal to 0.001). Conclusions: These findings showed large differences between leptin concentrations in normal and obese subjects; a progressive increase in leptin concentration with increasing body mass index. These results strongly support an important role for leptin in human metabolism and obesity. Leptin may simply reflect the size of adipose. tissue stores.