To elucidate a mechanism and clinical implications of chest pain and ST segment depression during exercise in patients with hypertrophic cardiomyopathy (HCM), we investigated myocardial lactate metabolism during atrial pacing in 18 patients with HCM and 7 control subjects with normal coronary arteriograms. At an average peak pacing rate of 146 beats/min, 11 patients with HCM showed the lactate extraction ratio decreasing to less than 5%, and 6 of them produced lactate, suggesting the development of myocardial ischemia. These 11 patients with abnormal lactate metabolism demonstrated ST segment depression (82%) and chest pain (73%) during pacing and also presented abnormal results (55%) on an exercise stress test. These abnormal findings were not observed in the other 7 patients who had ratios of 5% or more at peak pacing. These observations suggest that ST segment depression and chest pain are manifestations of myocardial ischemia even in patients with HCM who have normal coronary arteriograms, and that patients with pacing induced abnormal lactate metabolism are at an increased risk of developing myocardial ischemia during exercise.