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SUMMARY Four hundred and forty unrelated British Caucasoid patients with rheumatoid arthritis (RA) have been HLA typed for class I and class II antigens. Analyses of HLA antigen associations were performed on the overall group and in patient subsets selected according to particular disease parameters or sex, or both. The results confirm previously reported positive associations of HLA-DR4, Dw4, and DRw53 and negative associations of HLA-DR2 and DR7 with RA. Patients subsets with severe erosions, seropositivity, and features of extra-articular disease showed a stronger association, also confirming earlier reports. The link between HLA and disease severity was emphasised by a significant trend of increased Dw4 frequency with increasing severity of radiological erosions. In addition, a positive association of RA with HLA-A2 was observed and a strong negative association with DR3. The frequency of HLA-B27 was significantly increased in patients with subluxation of the spine. Differences were observed between male and female patients in relation to the HLA association. In men an increase in the frequency of the haplotype HLAIDw4/DR4/Bw62/Cw3/A2 was observed. This showed no relationship with parameters of disease severity other than extra-articular disease. In women only class II antigens (DRw53/Dw4/DR4) showed an increased frequency. This increase was strongly associated with disease severity. A significant decrease of this class II association was observed with increasing age of disease onset; this was not seen in men.Key words: HLA antigen associations, disease severity, seropositivity, erosions, subluxation of the spine, extra-articular disease, age of onset.Rheumatoid arthritis (RA) is a relatively common condition, of which the aetiology remains unknown and the basis for susceptibility in individuals is still unclear. A major advance in our understanding of RA development came with the observation that certain HLA antigens were strongly associated with this disease. These antigens include HLA-Dw4l DR4,2 and DRw53 (MT3).3 No association with HLA-A or B locus antigens was found in the early studies,4 5 though several later reports suggested other HLA antigen associations.6In most of the reported studies the frequency of DR4 in RA patients is within the range 50-75%,

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