Ventricular electrical instability and sudden death in mitral valve prolapse (MVP) have been related to mitral valve regurgitation and left ventricular dysfunction, autonomic nervous system abnormalities, or underlying cardiomyopathy. The aim of the present study was to assess the frequency, nature and pathophysiologic significance of histologic myocardial abnormalities in young patients with apparently isolated MVP and sudden cardiac death. Among 163 cases of sudden cardiovascular death in young people, MVP was the only cardiac pathology found at postmortem gross examination in 17 (10%) (12 females and 5 males) aged 14 to 35 years, mean 24. In 12 cases sudden death occurred at rest (during pregnancy in 2). MVP was diagnosed during life in 8 patients, 6 of whom had experienced palpitations and/or syncope, and 3 had premature ventricular beats. In every case, postmortem gross examination revealed "floppy" mitral valve leaflets with marked myxoid degeneration, and no other cardiovascular pathology. Cardiomegaly with left chamber enlargement was observed in 5 cases (mild in 3 and moderate in 2). In 12 cases (70%), histopathologic study disclosed myocardial abnormalities which consisted of focal myocardial atrophy and fatty replacement of the right ventricular wall (mostly the outflow tract) in 9 cases, left ventricular myocardial disarray (without hypertrophy) in 2, and lymphocytic infiltrates in one. "Foetal" dispersion of specialized atrioventricular junction and fasciculoventricular Mahaim's fibers were found in 2 cases. In conclusion, apparently isolated MVP was found in nearly 10% of sudden cardiovascular fatalities in young people. Most young sudden death victims with MVP were asymptomatic females without significant mitral valve regurgitation. In more than two-thirds of the cases, histopathologic examination evidenced underlying silent but potentially arrhythmogenic myocardial substrates, mostly consisting of segmental right ventricular cardiomyopathic changes.