Objective: Circulating leptin levels correlate positively with the degree of obesity and prolonged hyperinsulinaemia increases serum leptin levels. Moreover, insulin secreting b-cells express functional leptin receptors indicating a functional relationship between leptin and insulin. The aim of this study was to examine the relationship between fasting serum leptin levels and measures of insulin sensitivity and b-cell function in a population-based sample of 380 young healthy Caucasians. Design and Methods: Multiple regression analysis was employed to analyse the relationship between fasting serum leptin levels and levels of fasting serum insulin, insulin sensitivity index and acute insulin response (AIR) in a population-based study of 380 young healthy Caucasians who underwent a combined intravenous glucose and tolbutamide tolerance test. Results and Conclusion: Serum leptin levels were positively correlated to measures of adiposity and were 3.2 times higher in women than in men (P < 0.00001). In multiple regression analyses adjusting for age, percentage body fat, waist circumference and maximal aerobic capacity, a significant positive correlation was observed between the fasting serum leptin concentrations and both fasting serum insulin levels (P < 0.0001) and AIR (P = 0.014) for women. No significant interrelation of these variables was found in men. However, for both genders a significant negative correlation was observed between fasting serum leptin levels and measures of insulin sensitivity index (P = 0.007).