Juvenile idiopathic arthritis (JIA) is an HLA-associated rheumatic disease with onset in childhood. We recently reported that allele 5 at microsatellite D6S265 in the HLA class I region is associated with JIA, independent of linkage disequilibrium with the high risk DR8-DQ4 haplotype. In the present study, we investigated whether alleles at D6S265, or other markers in this region, also modify the risk for JIA on other haplotypes, i.e., DRB1*1301-DQB1*0603 or DRB1*1101/4-DQB1*0301. We observed a significant association with allele 6 at D6S265 on the DRB1*1301-DQB1*0603 haplotype. We also noted an association with allele 3 at D6S265, when carried on the DRB1*1101/4-DQB1*0301 haplotype. Our results further support an additional JIA susceptibility gene in the HLA class I region in linkage disequilibrium with alleles at D6S265.