Patients with hypertrophic cardiomyopathy may present a wide spectrum of clinical and morphologic manifestations. Although some characteristics of the natural history of these patients are well known, the initial presentation and subsequent clinical course of certain subgroups are not yet well defined. To further our understanding of the natural history of hypertrophic cardiomyopathy, we analyzed 31 middle-aged patients (35 to 55 years), who initially presented to our institution with no or minimal symptoms. Another group of 30 age and sex-matched patients, but in this case symptomatic (NYHA functional class II), was utilized as a control group for the purpose of morphologic comparison. Our data suggest that those patients with hypertrophic cardiomyopathy who do achieve middle-age without developing important symptoms, usually show a relatively benign long-term clinical course, predominantly nonobstructive form, and mild left ventricular hypertrophy in which the majority of patients have a localized distribution of left ventricular hypertrophy.