We studied the association of human leukocyte antigen (HLA)-DRB1 and HLA-DQB1 alleles and HLA haplotypes with juvenile rheumatoid arthritis (JRA) in 65 patients and 65 controls from Colombia. The JRA subsets were distinguished on the basis of criteria established by the American College of Rheumatology. Two alleles were associated with protection, HLA-DRB1*1501 (p = 0.002) and HLA-DRB1*1402 (p = 0.01). HLA-DRB1*1602 (p = 0.0000002) was associated with susceptibility for systemic JRA and HLA-DRB1*1104 (p = 0.0002) for pauciarticular JRA. Amino acid sequences at residues 70-74 of DRB1 chain shared by HLA-DRB1 alleles (shared epitomes) were also informative. The polyarticular JRA subset revealed association with (70)QRRAA(74), which includes HLA-DRB1*04, 01, and (70)DRRAA(74), which includes DRB1*1601, 1602, 1101, and 1104. Two new findings of interest were the association of the haplotypes DRB1*1104, DQB1*0301(p = 0.0002) with pauciarticular JRA and DRB1*1602, DQB1*0301 (p = 0.0000002) association with systemic JRA. The DRB1 alleles of these two haplotypes share the epitope (70)DRRAA(74)and were associated with both the pauciarticular and the systemic subset of JRA. Our results suggest that studies of disease susceptibility in populations of admixed genetic background should take into account the contribution of different ethnic groups or nationalities in the recruitment of controls and patients studied in order to rule out genetic stratification.