D8/17, a B cell alloantigen, and its occurrence with DR/DQ antigens was examined in 54 patients with rheumatic heart disease and matched North Indian controls. Thirty-four patients (62.9%) carried D8/17 as compared with a frequency of 12.5% in controls (chi 2 by Yates', 18.75; p less than 0.0001). A marginally increased frequency of human leukocyte antigen (HLA)-DR3 (44.2% vs. 28.8%) and a significantly reduced frequency of HLA-DR2 (21.1% vs. 46.6%; p less than 0.005) was observed in patients as compared with controls. However, the most significant positive association was observed with HLA-DQw2 (63.4% in patients and 31.5% in controls; chi 2 by Yates', 9.85; p less than 0.005). The DQw2 association was significant only in the D8/17-positive patients. These observations suggest that the disease susceptibility gene in rheumatic heart disease may be nearer to the HLA-DQ locus than to the HLA-DR.