Autoimmune mechanisms are likely to participate in the pathogenesis of a subgroup of dilated cardiomyopathy. These mechanisms involve the elaboration of autoantibodies against cardiac proteins as well as abnormal lymphocyte regulation. The presence of autoantibodies against β-adrenoceptors correlates with the human leukocyte antigen (HLA)-DR4/1 phenotypes and specific T-cell receptor haplotypes. In addition, histidine at position 36 of the HLA-DQβ1 gene is associated with the presence of clinically manifest dilated cardiomyopathy. Components of the major histocompatibility complex (MHC) may thus serve as markers for the propensity to develop immune-mediated myocardial damage.