Prostaglandin E1 (PGE1) has been used prior to operation in 28 neonates (0 to 30 days) with congenital heart disease (CHD). The patients were divided into two groups. Group I consisted of 19 neonates with CHD resulting in marked cyanosis. Thirteen patients had pulmonary atresia, three had tetralogy of Fallot, and three had complex defects with pulmonary stenosis. All patients were markedly hypoxemic. The average oxygen saturation was 41%. PGE1 infusion, 0.1 mcg/kg/min, was successful in 17 of 19 patients, as it resulted in an increase in oxygen saturation from 41% to 79%, average increase 38%. Two patients did not respond to PGE1 infusion. One was 30 days of age and the other had no patient ductus arteriosus. All of the patients underwent a palliative shunt procedure. There were three hospital deaths in this group. No patient died of hypoxemia. Group II consisted of nine patients whose CHD was predominantly that of aortic obstructive disease with clinical manifestations of cardiac failure, hypoperfusion, and acidemia. Six of these patients had complicated coarctation of the aorta. Three patients had interruption of the aortic arch. The pH of these patients averaged 7.19. PGE1 infusion resulted in improvement of the pH to average of 7.37, improvement of congestive heart failure, and reappearance of femoral pulses. One patient failed to respond. All patients in Group II underwent operation. There were three hospital deaths in this group. No patient died intraoperatively. PGE1 infusion is a valuable aid to surgical treatment of desperately ill neonates with both cyanotic and acyanotic forms of CHD.