Starting with the historical background and ending with the most recent data obtained by DNA typing, using PCR and oligonucleotide probes, the role of HLA antigens in rheumatoid arthritis (RA) and in several forms of juvenile arthritis (JA) is reviewed. RA is thought to be associated with an epitope of the third hypervariable region of DRB1 which is shared by several alleles including DR4-Dw4, Dw14, Dw15, DR1, DRw14.2, and DRw10. Rheumatoid factor-positive JA is also associated with DR4, but in rheumatoid factor-negative JA DR4 is absent, or markedly decreased, suggesting that it has a protective effect. Typing for the HLA-DP alleles has confirmed the association of pauciarticular JA with DPBI*0201. Recent studies in the author's laboratory have shown that DPB1*0301 is the main susceptibility factor for rheumatoid factor-negative polyarticular onset JA. It is of interest that also adult rheumatoid factor-negative RA patients have an increase of DPB1*0301, suggesting that these two clinical subsets may represent related diseases.