Cardiomyopathy (Cm), a rare form of cardiac disease in infancy, is receiving increasing attention stimulated by the availability of endocardial biopsy and new forms of therapy. Population-based information on frequency of occurrence, types, and maternal and infant characteristics of this diverse group of heart muscle disorders has been obtained in the course of an etiologic study on cardiovascular disease in infancy. The Baltimore-Washington Infant Study (BWIS) enrolled 2659 infants with heart disease and 2801 control infants between January 1, 1981 and March 31, 1987, a 6-year prevalence of 4.46/1000 live births. Fifty-six infants had cardiomyopathy, in the absence of a structural defect (prevalence 1/10,000). The cases were classified clinicopathologically as follows: dilated Cm (n = 17), hypertrophic Cm (n = 26), tumor (n = 5), endocardial fibroelastosis (n = 5), glycogen storage (n = 1), mucocutaneous lymph node syndrome (n = 1), and infarction (n = 1). Eleven syndromic associations and six metabolic disturbances indicate genetic risk factors. Some of the same syndromes occurred in other infants who had structural cardiac abnormalities. This overlap suggests that embryonic myocardial disease might sometimes be responsible for altered cardiac structures, possibly secondary to hemodynamic changes. Familial myocardial disease occurred in two infants with hypertrophic Cm. The Cm group did not differ by race and sex from controls, but the mothers were of lower educational and occupational status with less private care and with later registration for pregnancy care. The descriptive epidemiology of this population-based case group provides evidence of greater etiologic heterogeneity than has been shown in clinical reports.