We investigated the possible association between the IL-6 promoter polymorphisms, at positions -622 and -174, and susceptiblity to, and/or outcome of, rheumatoid arthritis (RA). A total of 163 patients with RA and 157 healthy controls were genotyped for IL-6 using a PCR-RFLP method. The -622 and -174 alleles were in complete linkage disequilibrium. No difference was observed in the distribution of IL-6 promoter genotype or allele frequencies between RA patients and controls. However, a significant difference in the mean age at disease onset between IL-6 genotypes was observed. The present data appear to rule out an important role of IL-6 promoter polymorphisms in the susceptibility to RA. However, IL-6 genotypes may contribute to the pathogenesis of the disease by influencing the age at disease onset.