Although considerable information is available concerning the clinical features and natural history of asymmetric septal hypertrophy (ASH) in adults, little is known of this disease in children. The clinical characteristics and course of 46 children with ASH, who were evaluated at the National Heart and Lung Institute, have been analyzed. Twenty-four children had obstruction to ventricular outflow; 22 children had no obstruction to ventricular outflow, including 11 patients without overt manifestations of cardiac disease other than echocardiographic evidence of ASH. Thirty-five of the 46 children have been followed for one to 16 years (average 7.4 years). These latter children represent that subgroup of patients with ASH referred to the National Heart and Lung Institute and diagnosed prior to the general availability of echocardiography. The clinical course of these patients was variable. Fourteen (40%) of the 35 patients improved or remained stable, including four patients who received propranolol. Ten (29%) of the 35 patients deteriorated clinically and 11 (31%) of the 35 patients died suddenly (4% mortality per year). Two of the patients who died suddenly had previously undergone operation (six and 13 years previously) with resultant abolition of the outflow gradient; four others were taking propranolol. Neither symptomatology, electrocardiographic abnormalities, heart size, left ventricular ejection or upstroke time, magnitude of outflow gradient, or left ventricular enddiastolic pressure proved predictive of sudden death. Excluding patients who had previous operation, eight (40%) of 20 patients with obstruction who were followed long term and one (9%) of patients without outflow obstruction died suddenly. Thus, the clinical and hemodynamic spectrum of ASH in childhood is broad. However, deterioration in clinical condition or sudden death has been relatively common in children with overt signs of cardiac disease.