Leptin levels are strongly related to total body fat. It is however not yet clear if leptin is also related to visceral fat accumulation or not. In this study, we investigated whether leptin is also associated with body fat distribution and if this association is different in men and women. Leptin was measured in 143 obese subjects (118 women and 25 men) with a body mass index (BMI) greater than 28. Also weight, skinfolds, waist-to-hip ratio (WHR), fat mass by bioimpedance analysis (BIA) were measured, and abdominal visceral and subcutaneous fat were determined by CT scan. Leptin levels were significantly related with BMI, with fat mass (in kg and percentage body fat) as measured by BIA and skinfolds, and with total abdominal fat mass and subcutaneous fat measured by CT scan. No association was found with visceral fat, waist circumference or WHR. In men and women separately, however, a correlation with visceral fat existed. After correction for total body fat, the correlation remained significant only with subcutaneous fat in women. Multiple regression analyses pointed out that percentage body fat was the most important determinant of leptin for all subjects, while for women subcutaneous fat was the most important parameter, and for men alone total abdominal fat. These results suggest that subcutaneous fat seems to be an important factor related to leptin levels.