HLA-DR antigens were determined in 111 patients with classic or definite rheumatoid arthritis. HLA-DR4 was significantly (P corr. less than 10(-6] increased in patients with rheumatoid arthritis (54%) compared with controls (23.2%). HLA-DR 5 was decreased in rheumatoid arthritis (12.6% vs 26.4% of controls); however, the corrected P value was not significant. There were no significant differences with regard to various clinical, radiological and serological parameters between HLA-DR 4 positive and negative patients. However, a milder course of rheumatoid arthritis was observed in DR 7 positive patients: Patients with this antigen were associated significantly with seronegativity and low titers of IgM-rheumatoid factor. Despite a similar disease duration patients with DR 7 had a significantly lower number of joints with inflammatory arthritis (synovitic swelling with limitation of movement) and developed less frequently severe radiological changes as joint ankylosis than DR 7 negative patients. In addition to the well known association between rheumatoid arthritis and HLA-DR 4, our data indicate that HLA-DR 7 may have a protective effect on the course of rheumatoid arthritis.