Prostaglandin E1 (PGE1) has been used for successful palliation in nine infants with congenital heart disease. Seven patients had pulmonary atresia with ductal-dependent pulmonary blood flow. In this group, systemic O2 saturation increased from a mean value of 45% to 79% after infusion of PGE1, and surgical palliation was successfully done with the infants in stable condition, without hypoxemia or acidemia. An additional patient with coarctation of the aorta had marked ductal dilatation after PGE1 infusion, as indicated by umbilical artery pulse pressure. The coarctation was repaired, with the infant in stable condition. The final patient had neonatal tricuspid insufficiency with right-to-left atrial shunting. Systemic O2 saturation was improved after PGE1 infusion, though the ductus was closed. The improved oxygenation was believed to be due to a reduction in pulmonary vascular resistance by PGE1. Prostaglandin E1 provides a powerful new tool for palliation of critical congenital heart disease in infants whose ductal constriction can markedly influence their clinical status.