Apical hypertrophic cardiomyopathy, a very common disorder in Japan, is characterized by giant negative T waves on the electrocardiogram and abnormal apical hypertrophy on the ventriculogram. This histocompatibility complexes (HLA-A, -B, -C, -DR) of 20 unrelated patients with apical hypertrophic cardiomyopathy (18 male, 2 female) were examined. There was no significant difference in the frequency of HLA-A, -B, -C antigens between patients and controls (n = 100). However, HLA-DR 2 was more frequent in patients with apical hypertrophic cardiomyopathy (65.0%) than controls (33.0%) (p < 0.01). We conclude that apical hypertrophic cardiomyopathy might be associated with genes in the HLA-DR region and that genetic factors linked to HLA play a role in the pathogenesis of this disease.