To assess the association between HLA-DRB1 and the pathogenesis of rheumatoid arthritis (RA) in the Japanese population, we typed for HLA-DRB1 alleles in 852 Japanese patients. An analysis of HLA-DRB1 allele associations was performed on the overall group and in three disease subsets of adult-onset RA, classified according to the extent of joint destruction evident on plain radiograms, i.e. least erosive subset (LES), more erosive subset (MES) and most erosive subset with mutilating disease (MUD). The Japanese RA patients with positively associated with DRB1*0101 and *0405, and negatively associated with DRB1*0701, *0802, *1302 and *1405. DRB1*0101 was associated more strongly with a milder disease subset and the relative risk (RR) was 1.9, 1.5 and 1.2 for LES, MES and MUD, respectively. On the other hand, DRB1*0405 was associated more strongly with a more severe disease subset, the RR being 1.8, 4.0 and 4.3 for LES, MES and MUD, respectively. These findings suggest that RA is a heterogeneous disease, not only clinically, but also in terms of its immunogenetic background, and that HLA-DRB1 can be a useful prognostic factor for RA.