Disopyramide reduces the subaortic pressure gradients and improves the clinical symptoms of patients with hypertrophic obstructive cardiomyopathy. Changes in coronary hemodynamics and vasodilator reserve in response to this agent have not been evaluated in such patients. To assess the acute effects of intravenous administration of disopyramide on coronary hemodynamics, microvascular dilatory capacity, and balance between myocardial oxygen supply and demand in hypertrophic obstructive cardiomyopathy, we examined 12 patients using an intravascular Doppler catheter and spectral analysis. Intravenous disopyramide 100 mg over 10 min caused mild increases in heart rate and aortic systolic pressure and a significant fall in left ventricular systolic pressure, resulting in a 13% decrease in the product of heart rate and left ventricular systolic pressure (from 1.13 ± 0.18 × 10<sup>4</sup> before disopyramide to 0.98 ± 0.17 × 10<sup>4</sup>beats/min × mm Hg 10 min afterwards; p < 0.05) and a reduction in the resting peak systolic pressure gradients of the left ventricular outflow tract. There was a 14% reduction in coronary blood flow (from 93.5 ± 13.2 to 80.3+ 11.6ml/min; p < 0.05) with an increase in coronary resistance (from 0.94 ± 0.16 to 1.23 ± 0.21 mm Hg/ml/min; p < 0.001). The index of coronary vasodilator reserve remained unchanged. These findings suggest that intravenous disopyramide causes a coronary vasoconstrictive effect without significantly changing the coronary microvascular dilatory capacity, but this effect may not be harmful to the balance between myocardial oxygen supply and demand in patients with hypertrophic obstructive cardiomyopathy.