OBJECTIVE: The obese (ob) gene encodes leptin which inhibits appetite and stimulates thermogenesis. Serum leptin concentrations are determined by total body fat mass, but the influence of visceral fat accumulation and other metabolic factors have not been clinically determined. METHODS: We determined the correlations between serum leptin concentrations and the total body fat mess, abdominal fat mass, abdominal Sat distribution (estimated by ultrasound), and circulating metabolic factors in 104 Japanese healthy subjects (11 men and 93 women). In addition, the effect of food restriction (30 kcal/kg desired body weight/day) for four weeks on serum leptin concentrations were also examined in 30 women. RESULTS: There was a significant correlation between serum leptin concentrations and total body fat mass (r = 0.708, P < 0.0001), the percentage of body fat (r = 0.561, P < 0.001), and the body mass index BMI, r = 0.630, P < 0.001). Serum leptin concentrations were correlated with the abdominal wall preperitoneal and subcutaneous fat pad thickness, but not the abdominal wall fat index (AFI). Serum leptin concentrations were also correlated with serum immunoreactive insulin (IRI), but not glucose, Or free fatty acid (FFA) concentrations. The weight less after food restriction for four weeks significantly (P = 0.016) reduced the serum leptin concentrations with a significant reduction of body fat mass, serum glucose, IRI and FFA concentrations. However, there was no significant correlation of the percentage change in serum leptin concentrations to that in body fat mass after food restriction. CONCLUSION: Serum leptin concentrations are well correlated with the total body dat mass in healthy subjects. Differences in abdominal fat distribution do not appear to be related to a difference in the in vivo leptin production from adipose tissue.