To examine the mechanism of myocardial ischemia in hypertrophic cardiomyopathy (HCM), coronary flow velocity was measured in the left anterior descending coronary artery (LAD) using a Doppler guide wire in 11 patients with HCM and in 8 normal controls. The average peak velocity (APV), percent increase of APV (%APV), and APV during systole (Vs) and diastole (Vd) were calculated at rest and during rapid atrial pacing. The APV in HCM reached a peak value at a heart rate of 90 beats/min, while in the controls the APV increased continuously until the heart rate reached 130 beats/min [%APV (130 beats/min); 103+/-30% in HCM vs 139+/-23% in controls, p<0.04]. During rapid atrial pacing, Vs in the controls increased, whereas Vs in HCM decreased further. During high-rate pacing, Vd in HCM reached a peak value at a heart rate of 90 beats/min, whereas in the controls, Vd increased continuously until the heart rate reached 130 beats/min. The acceleration rate of early diastolic flow was significantly lower in HCM than in the controls (1.85+/-0.66 vs 3.18+/-1.62 m/s2, p<0.03). This abnormal response might be due to an increase in the reverse systolic flow and a decrease in the diastolic flow, probably caused by a slow acceleration of early diastolic flow velocity in the LAD.