Obesity represents an expansion of adipose tissue (AT) mass and is closely related to insulin resistance and cardiovascular disease. Several hormonal signals have been shown to originate from AT, one of them being interleukin 6 (IL6), for which one third of circulating levels is accounted for by AT. To study the impact of the IL6 -174G/C polymorphism on obesity-related phenotypes, we genotyped a cohort of 270 French-Canadian men from the greater Quebec City area selected to cover a wide range of body fatness values. The IL6 -174G allele was more commonly observed among lean subjects (body mass index <25 kg/m(2), chi(2) = 7.27, P = 0.007 or waist-line <100 cm, chi(2) = 6.63, P = 0.01). When men were subdivided according to insulin and glucose levels at 180 min following the glucose load, using 160 pmol/l and 4.6 mmol/l, respectively, as cutoff points, the -174G allele was more frequently observed in groups with low concentrations of either insulin or glucose, P = 0.03 and P = 0.01, respectively. When comparisons between genotype groups were performed, -174G/G homozygotes presented the lowest waist circumference ( P < 0.05). In summary, this study showed that, in men, the IL6 -174G/C polymorphism is associated with some indices of body composition and parameters of glucose and insulin homeostasis.