There were 47 seriously-ill neonates with medical causes of respiratory distress and 10 infants with severe respiratory distress secondary to a congenital diaphragmatic hernia treated with tolazoline according to a strict protocol designed to manage persistent fetal circulation (PFC). Of the 47 infants, 28 (60%) had a positive response defined as an increase in the pO2 greater than or equal to 24 mm Hg within 4 hr of beginning the drug. Of 7 infants, 4 with congenital diaphragmatic hernia had a positive response. The mean increase in the pO2 for the 47 infants was statistically significant (p less than .05). Of the 47 infants with medical disorders, 27 survived (survival 57%), whereas only 2 of the 10 infants with congenital diaphragmatic hernia and severe persistent fetal circulation survived (survival 28%). Erythema (60%), hematest positive gastric aspirates (55%), thrombocytopenia (45%), hyponatremia (40%) and increased gastric aspirates (36%) were the most common adverse effects occurring during tolazoline infusion. Hypotension occurred in nine cases, but was transient. Of the 27 survivors, 20 with medical causes of persistent fetal circulation were evaluated at age 1 yr. Eighty percent of these infants studied were considered normal as defined by an MDI and PI of the Bayley Scales of greater than or equal to 70. These data suggest that tolazoline is a useful adjunct in the management of neonates with PFC. In addition, tolazoline was more effective in mechanically ventilated neonates treated with respiratory paralytic agents. Although tolazoline resulted in a significant improvement in the paO2 in 4 infants with congenital diaphragmatic hernia, it did not appear to improve mortality in these infants.