To evaluate the effects of acute afterload reduction, hydralazine, 0.2 mg/kg, was administered at cardiac catheterization to seven infants who had a large ventricular septal defect (VSD). The infants were 2.5 - 11 months old (mean 5.1 months). Before and 5, 15, 25 and 35 minutes after hydralazine, aortic, pulmonary capillary wedge, pulmonary artery, right atrial and superior vena caval pressures and saturations, heart rate and oxygen consumption were measured. Hemodynamic effects were noted after 5 minutes but were most pronounced 35 minutes after hydralazine. Prehydralazine baseline data were therefore compared with values 35 minutes after hydralazine. Pulmonary flow did not changes, but systemic flow increased significantly (4.5 +/- 0.2 to 6.7 +/- 0.5 liters/min/m2 [mean +/- SEM], p less than 0.001). The pulmonary-to-systemic flow ratio decreased by 32% (3.4 +/- 0.4 to 2.3 +/- 0.2, p less than 0.001) and the absolute left-to-right shunt decreased by 24% (10.8 +/- 1.3 to 8.2 +/- 1.2 liters/min/m2, p less than 0.01). Hydralazine caused a significant decrease in systemic resistance (13.9 +/- 0.7 to 9.5 +/- 0.7 U, p less than 0.001). Pulmonary resistance, aortic, pulmonary artery and pulmonary capillary wedge pressures, heart rate and oxygen consumption did not change after hydralazine. Right atrial pressure decreased slightly (4.0 +/- 0.6 to 2.4 +/- 0.6 mm Hg, p less than 0.05). In conclusion, hydralazine caused a significant increase in systemic blood flow and a significant decrease in both pulmonary-to-systemic flow ratio and absolute left-to-right shunt in seven infants with a large VSD. These effects appear to be related to the decrease in systemic resistance that occurred with hydralazine. Although limited to the acute setting, these findings suggest that hydralazine may be beneficial in the management of infants with a large VSD.