Two families with familial muscular subaortic stenosis have been studied. Hemodynamic data in 2 cases and the operative findings of 1 case are described. Autopsy findings of 3 cases have been presented. Clinical findings indicate at least 3 additional cases in 1 family and 5 in the other. The pedigrees of both families have been discussed. The incidence of this lesion in each family over 3 generations suggests that the defect is related to Mendelian dominant inheritance. To our knowledge, this is the first report of cases of familial heart disease compatible with transmission by a Mendelian dominant gene. The importance of differential diagnosis of this disease from other types of aortic or subaortic stenosis prior to surgery has been stressed, since no operation has been devised for this lesion. The distinguishing clinical features include the apical and lower left sternal border location of the systolic murmur, the absence of poststenotic dilatation of the ascending aorta, the absence of calcification of the aortic value, the absence of a murmur of aortic insufficiency, and the strong family history suggesting a familial trait.