The authors evaluated the safety and efficacy of liquid ventilation with perfluorocarbon in four newborns with congenital diaphragmatic hernia and severe respiratory failure, who were on extracorporeal life support (ECLS). After 2 to 5 days on the ECLS, perflubron was administered into the trachea until the dependent zone of the lung was filled. The first dose was 6 +/- 1 mL/kg (range, 5 to 8 mL/kg). Gas ventilation of the perflubron-filled lung was performed (partial liquid ventilation). The administration of perflubron was repeated daily for 5 to 6 days, with total cumulative doses of 36 +/- 8 mL/kg (range, 26 to 44 mL/kg). A significant increase in PaO(2) (P = .027 by repeated-measures analysis of variance [ANOVA]), a trend toward an increase in arterial oxygen content (P = .052 by repeated-measures ANOVA), and a significant increase in specific static total pulmonary compliance (P = .007 by repeated-measures ANOVA) were observed after administration of the daily dose of perflubron. PaCO(2) data showed a decreasing trend (P = .08 by repeated measures ANOVA). The authors conclude that perflubron can be safely administered into the lungs of newborn patients with congenital diaphragmatic hernia and severe respiratory failure, and it may be associated with improvement in gas exchange and pulmonary compliance.