Interleukin-1 (IL-6) is an important mediator of inflammatory response in the respiratory tract during an infection, and the action of IL-6 is mediated by an IL-6 receptor. Several polymorphisms in the IL-6 and IL-6R genes have been associated with different inflammatory disease states. We studied the association between 2 IL-6 (IL6A and IL6B) and 5 IL-6R gene polymorphisms (IL6R1 to IL6R5) and respiratory infections in 511 Finnish military recruits whose respiratory infectious episodes were followed during 6 months of service. A promoter polymorphism of the IL-6R gene, IL6R1 (-183G/A), and two intron 1 polymorphisms, IL6R2 (A/G) and IL6R3 (T/A), were associated with infections. The strongest associations were found for the IL6R1 and IL6R2 polymorphisms, which were in the same linkage disequilibrium block. Conscripts with the A/A (IL6R1), G/G (IL6R2), and A/A (IL6R3) genotypes had an increased risk for respiratory infections during service as follows: odds ratio (OR) 1.72, 95% confidence interval (CI) 1.35-2.19; OR 1.66, 95% CI 1.23-2.26; and OR 1.23, 95% CI 0.98-1.55, respectively. IL-6 gene polymorphism IL6A (-174C/G) was associated with infections only in combination with an IL-6R polymorphism. Our data suggest that polymorphisms in the 5' area of the IL-6R gene may be associated with increased susceptibility to respiratory infections.