Hypertrophic cardiomyopathy and mitral valve prolapse are both conditions that may be genetically transmitted and incur a risk for sudden cardiac death. Although the small left ventricular cavity and distorted geometry characteristic of hypertrophic cardiomyopathy might suggest a predisposition to mitral valve prolapse, the frequency with which these two entities coexist and the potential clinical significance of such an association are not known. To further define the relation of hypertrophic cardiomyopathy and mitral valve prolapse, 528 consecutive patients with hypertrophic cardiomyopathy were studied by echocardiography. Patients ranged in age from 1 to 86 years (mean 45); 335 (63%) were male. Unequivocal echocardiographic evidence of systolic mitral valve prolapse into the left atrium was identified in only 16 (3%) of the 528 patients. The mitral valve excised at operation from three of the patients had morphologic characteristics of a floppy mitral valve, which was judged to be responsible for the echocardiographic findings. Occurrence of clinically evident atrial fibrillation was common in patients with hypertrophic cardiomyopathy and mitral valve prolapse (9 [56%] of 16). Hence, in a large group of patients with hypertrophic cardiomyopathy, the association of echocardiographically documented mitral valve prolapse was uncommon. The coexistence of mitral valve prolapse in patients with hypertrophic cardiomyopathy appears to predispose such patients to atrial fibrillation.