Administration of sodium nitroprusside increases the cardiac output and decreases the pulmonary wedge pressure in patients with left ventricular failure. Drugs suitable for long-term oral administration have not been as effective as intravenous therapy with sodium nitroprusside. The authors compared the hemodynamic effects of combined oral therapy with hydralazine and isosorbide dinitrate (100 mg of hydralazine plus 10 to 50 mg of chewable isosorbide dinitrate) to the effects of intravenous therapy with sodium nitroprusside in 15 patients with congestive heart failure (class 3 to 4) due to cardiomyopathy. Therapy with sodium nitroprusside reduced the mean arterial pressure by 11.3 mm Hg and the pulmonary wedge pressure by 10.4 mm Hg while increasing the cardiac index by 0.72 L/min/sq m. The combined oral therapy also reduced the mean arterial pressure by 12.0 mm Hg and the pulmonary wedge pressure by 12.0 mm Hg while increasing the cardiac index by 0.81 L/Min/sq m in the same patients. All changes were significant (P < 0.001), and there were no differences between the two types of therapy. Both regimens reduced the right atrial pressure and dilated the veins of the forearm. Compared to administration of sodium nitroprusside, therapy with hydralazine alone lowered the pulmonary pressure less but raised the cardiac index as much; therapy with isosorbide dinitrate alone lowered pulmonary pressures as much as administration of sodium nitroprusside but raised the cardiac index less. Thus, by dilating both arteries and veins, combined oral therapy with hydralazine and isosorbide dinitrate closely mimics the hemodynamic effects of administration of sodium nitroprusside and may be useful for long term vasodilator therapy.