Patients with hypertrophic cardiomyopathy frequently experience chest pain that occurs with variable threshold of onset and is often prolonged in duration. The study was designed to evaluate the effect of a pharmacologic vasoconstrictor agent, ergonovine, on the coronary vasculature of patients with hypertrophic cardiomyopathy. Twenty-four patients with hypertrophic cardiomyopathy and a history of angina pectoris despite normal epicardial coronary arteries underwent a study of coronary flow, and myocardial function and metabolism. During pacing to an average heart rate of 133, 18 of the 24 patients experienced their typical chest pain. During pacing after the administration of ergonovine, 22 of 24 patients experienced chest pain. Despite a significantly higher blood pressure following ergonovine administration, the coronary flow at an average pacing rate of 138 beats/min was significantly lower than during pacing to a similar heart rate prior to administration of ergonovine. There was no epicardial coronary artery narrowing during coronary angiography after ergonovine administration. Thus, peak coronary flow decreases with ergonovine in patients with hypertrophic cardiomyopathy, probably due to vasoconstriction of a maximally dilated microvascular bed, or vasoconstriction of prearteriolar small coronary arteries. Small vessel coronary vasoconstriction may explain many of the atypical features of angina pectoris in patients with hypertrophic cardiomyopathy, causing pain at rest or during variable levels of effort.