Leptin is proposed to be involved in regulation of body weight. Only little information is available on leptin concentrations in individuals with impaired glucose tolerance (IGT). The aim of the present study was to assess the effect of body fat distribution and weight reduction on serum leptin levels in a prospective setting in IGT subjects. Sixty-nine individuals with impaired glucose tolerance aged 45-64 years participated in this prospective study. Serum leptin levels were about 300% higher among females than among males, despite an only 30% higher fat percentage in females. A close association between degree of obesity and leptin concentrations was observed in both sexes. The correlation coefficient between fat mass and leptin concentration ranged between r = 0.467- 0.817 (p< 0.001 - 0.01). A close correlation between degree of weight loss and decrease in leptin concentrations was observed in both sexes. A 10.1 kg (9.6%) decrease in body weight among females was associated with a 32% decrease in leptin concentrations. The corresponding value among males for an 8.0 kg (8.6%) decrease was 29%. Changes in leptin concentrations were best explained by changes in fat mass among both males and females. Body fat distribution was also of importance, especially among females. Gender associated differences in leptin concentrations appear to be largely influenced by gender differences in body fat distribution.