Sudden death is a recognized complication in symptomatic patients with hypertrophic cardiomyopathy. However, its occurrence in patients with no or transient previous cardiac symptoms presents a particularly challenging diagnostic and therapeutic dilemma. Therefore, 26 patients with hypertrophic cardiomyopathy whose death was the first definitive manifestation of cardiac disease were evaluated. Their ages ranged from 8 to 49 years (mean 18) and 23 were less than 25 years of age; 19 were male and 7 female. Of the 26 patients, 13 died during or immediately after moderate or severe physical exertion. Of 12 patients with previous cardiac catheterization, 6 had no or a small left ventricular outflow tract gradient under basal conditions and 6 had an outflow gradient of 50 mm Hg or greater. Left ventricular end-diastolic pressure was elevated in nine patients, and the ventricular septum was moderately to severely thickened (17 mm or more) in all patients. The electrocardiogram was abnormal in all 19 patients studied before death. Thus, sudden death may be the first definitive manifestation of cardiac disease in some patients with hypertrophic cardiomyopathy. Although the effects of patient selection in this study group cannot be excluded, sudden death was common in children and young adults and was often related to physical exertion; each patient showed a distinctly abnormal electrocardiogram and moderate to severe ventricular septal thickening.