Hypertrophic cardiomyopathy is a newly recognized, potentially fatal complication of ACTH therapy. We report the clinical, echocardiographic, and pathologic findings of an infant who was treated with ACTH for seizure disorder and subsequently developed severe systemic hypertension. Echocardiography revealed marked cardiac hypertrophy with disproportionate septal hypertrophy. Decreasing the dose of ACTH reduced the systemic blood pressure, but the cardiac hypertrophy progressed and the child subsequently died. Children who develop hypertension during ACTH therapy should be considered at risk for hypertrophic cardiomyopathy and should undergo routine echocardiographic evaluation.