To clarify the pathogenesis of chest pain in patients with cardiomyopathies, we compared coronary blood flow and other indicators of ischemia at rest and during pacing-induced tachycardia in nine patients with cardiomyopathy (four hypertrophic and five congestive) and in five control subjects. Coronary blood flow was reduced at rest and during pacing in cardiomyopathy patients compared with controls. In patients with hypertrophic cardiomyopathy, pacing induced chest pain in all, increased ST-segment depression in three patients and increased coronary venous lactate concentration. With pacing, two of five patients with congestive cardiomyopathy had chest discomfort and three had increased ST-segment depression, but coronary venous lactate concentration did not change significantly. In both groups of cardiomyopathies, the ratio of the systolic and diastolic pressure-time indexes tended to decrease more than in controls during pacing. Thus, myocardial perfusion is decreased in patients with cardiomyopathy, both at rest and during pacing. The changes detected during pacing point to subendocardial ischemia as the likely mechanism for angina in hypertrophic and possibly also in congestive cardiomyopathy.