HLA-DR5 is associated with a chronic iridocyclitis and juvenile rheumatoid arthritis with onset in early childhood. Previously published data provided indirect evidence for selective linkage between two HLA-B alleles and HLA-DR5. To test this observation further, 38 families, the probands of which have chronic iridocyclitis and juvenile rheumatoid arthritis, were HLA typed so that haplotypes associated with disease could be established. HLA-DR5 was linked to HLA-Bw44 or to HLA-Bw35 and to HLA-Cw4 in the majority of haplotypes obtained in the probands. Both HLA-Bw44, -DR5 and HLA-Bw35, -Cw4, -DR5 occurred more commonly in the proband haplotypes than in the control haplotypes. The frequency of the haplotype HLA-Bw44, -DR5 was 0.133 compared with 0.007 (X2 = 27.04, P less than 10(-6] and for HLA-Bw35, -Cw4, -DR5, it was 0.093 compared with 0.11 (X2 = 13.83, P = 0.0002). The relative risks were 20.77 and 9.23, respectively, versus 3.52 for HLA-DR5 alone. HLA-Bw44 occurred much more commonly in proband HLA-DR5 haplotypes (0.455) compared with control HLA-DR5 haplotypes (0.067) (X2 = 8.26, P less than 0.01). Not all HLA-DR5-bearing haplotypes predisposed equally to chronic iridocyclitis and early-onset pauciarticular juvenile rheumatoid arthritis.