Oral hydralazine has been shown to be effective in decreasing pulmonary arteriolar resistance and increasing cardiac output in some patients with primary pulmonary hypertension. To determine whether a similar response could be observed in patients with chronic cor pulmonale, the hemodynamic status before and after the oral administration of hydralazine (25 mg, then 50 mg every 6 hours for 48 hours) were evaluated in 12 patients at rest and in 8 during upright exercise. After hydralazine, there was an increase in cardiac output at rest, from 4.3 to 6.3 liters/min (p < 0.001), and reductions in arteriovenous oxygen difference, from 8.1 to 6.1 volume percent (p < 0.001), mean pulmonary arterial pressure, from 52 to 44 mm Hg (p < 0.01), and pulmonary arteriolar resistance, from 11.2 to 6.2 units (p < 0.0005). Similar hemodynamic changes occurred during exercise, including an increase in pulmonary arterial saturation from 27 to 39 percent (p < 0.001) and a decrease in total pulmonary resistance from 12.7 to 8.9 units (p < 0.01). Results of pulmonary function tests performed before and after hydralazine did not change with drug administration. These findings indicate that the lung vascular bed in some patients with cor pulmonale is capable of responding to hydralazine with a reduction in pulmonary resistance and an increase in cardiac output both at rest and during exercise.