Women of the Yakima Indian Nation, a northwest Native American population, are known to have an increased prevalence of a rheumatoid arthritis-like disease characterized by erosive arthritis, frequent involvement of metacarpophalangeal and wrist joints, and positive rheumatoid factor. These patients are frequently positive for antinuclear antibodies and often demonstrate adverse reactions to gold therapy. HLA antigens were determined for 29 Yakima Indians with this disease, but there was no increased frequency of either HLA-Dw4 or HLA-DR4, in contrast to other populations with rheumatoid arthritis. There was, however, a trend toward an increase in HLA-B40 and a decrease in HLA-DR8. The relative risk for rheumatoid arthritis in Yakima Indians was 2.53 in the presence of B40 and 0.28 in the presence of DR8.