We studied the association of the G-174C promoter polymorphism in the interleukin-6 gene (IL6) with total body fat and fat-free mass (FFM) in 242 men and women (IL6 genotypes: G/G, n = 87; G/C, n = 100; C/C, n = 55) across the adult age span (21-92 years). In men, but not women (significant genotype by sex interactions; p =.023-.048), the C/C group exhibited significantly lower total FFM than the G/G group (54.7 +/- 0.8 kg vs 57.2 +/- 0.7 kg, respectively, p =.020), as well as significantly lower FFM of the lower limbs compared with the G/G group (18.4 +/- 0.3 kg vs 19.8 +/- 0.3 kg, respectively, p =.004). No significant genotype differences were observed in total body fat mass in either men or women. The results indicate that the IL6 G-174C polymorphism is significantly associated with FFM in men but not women.