The distribution of class I and class II HLA antigens of 100 Turkish patients with rheumatic fever, 77 of whom had cardiac involvement, was examined. We compared the results with a control group of identical origin. The frequency of HLA A10 and HLA B35 antigens were found significantly higher in patients with rheumatic fever (p<0.05, p<0.01, respectively). The frequency of HLA A10 and HLA DRw11 in patients with cardiac involvement were significantly higher than in those without cardiac involvement (p<0.05, p<0.01, respectively). On the other hand, HLA Cw2 antigen frequency was found significantly higher in patients without cardiac involvement than in those with rheumatic heart disease (p<0.05). We support the concept that rheumatic fever is an immunological reaction to group A, beta hemolytic streptococci in individuals who have genetic predisposition.