Many patients with hypertrophic cardiomyopathy have signs and symptoms of myocardial ischemia and dysfunction. To determine the prevalence and extent as well as the clinical relevance of abnormal intramural coronary arteries, a histologic analysis of left ventricular myocardium obtained at necropsy was performed in 48 patients with hypertrophic cardiomyopathy and in 68 controls. In hypertrophic cardiomyopathy, abnormal intramural coronary arteries were characterized by thickening of the vessel wall and a decrease in luminal size. The wall thickening was due to proliferation of medial and/or intimal components, particularly smooth muscle cells and collagen. Of the 48 patients with hypertrophic cardiomyopathy, 40 (83%) had abnormalities of intramural coronary arteries located in the ventricular septum (33 patients), anterior left ventricular free wall (20 patients) or posterior free wall (9 patients); an average of 3.0 plus/minus 0.7 abnormal arteries were identified per tissue section. Altered intramural coronary arteries were also significantly more common in tissue sections having considerable myocardial fibrosis (31 of 42, 74%) than in those with no or mild fibrosis (31 of 102, 30%; p less than 0.001). In contrast, only rare altered intramural coronary arteries were identified in 6 (9%) of the 68 control patients, and those arteries showed only mild thickening of the wall and minimal luminal narrowing (abnormal arteries per section, 0.1 plus/minus 0.05; p less than 0.001). Hence, abnormal intramural coronary arteries with markedly thickened walls and narrowed lumens are present in increased numbers in most patients with hypertrophic cardiomyopathy at necropsy and they may represent a congenital component of the underlying cardiomyopathic process.