Necropsy studies were performed in 125 infants, 2 years old or less, with a variety of congenital heart malformations. Disproportionate ventricular septal thickening (septal-to-left ventricular free wall thickness ratio ≥1.3) was present in 31 (25%) of the 125 patients. In the majority of patients, an abnormal septal-to-free wall ratio did not appear to be manifestation of genetically transmitted hypertrophic cardiomyopathy, since: 1) marked disorganization of septal myocardium (involving ≥5% of the tissue section) was present in only five of the 31 patients with disproportionate septal thickening; and 2) echocardiographic studies in first degree relatives of four other patients with disproportionate septal thickening and normal septal architecture did not show asymmetric septal hypertrophy. The relatively high prevalence of septal-to-free wall ratios of 1.3 or greater in this population of infants with congenital heart disease appeared to be due in part to minor differences in ventricular wall thickness (in patients with relatively thin absolute wall thickness) which may produce particularly large deviations from unity in septal-to-free wall ration. Hence, 1) nongenetically transmitted disproportionate septal thickening is relatively common in infants with congenital heart diseases studied at necropsy; and 2) a septal-to-free wall ratio of ≥1.3 cannot be used as the sole criterion for identifying associated hypertrophic cardiomyopathy in infants with other congenital heart diseases, particularly if marked absolute septal thickening is absent.