To test the hypothesis that perfluorochemical (PFC) instillation may reduce the pulmonary trauma commonly associated with conventional gas ventilation, we studied 12 lambs with normal lungs and 10 with pulmonary hypoplasia secondary to congenital diaphragmatic hernia (CDH). We used mechanical ventilation for up to 3.5 h, with and without tracheal instillation of LiquiVent PFC liquid. At the end of experimentation lungs were fixed for morphometrical analysis of their components and pulmonary trauma was evaluated by measurement of the perivascular compression index (PCI = % perivascular emphysema/% vessels). In normal lungs good gas exchange and respiratory mechanics were obtained with all modes of ventilation, with no statistical difference in the index of pulmonary trauma with or without instillation of LiquiVent (P >0.05). In the hypoplastic lungs, tracheal instillation of PFC liquid after 30 min of conventional gas ventilation significantly improved PaCO2 (from 107+/-8 to 55+/-6 mmHg, P <0.05), pH (from 7.00+/-0.03 to 7.29+/-0. 04, P <0.05), compliance (from 0.08+/-0.01 to 0.25+/-0.03 ml/cmH2O . kg, P <0.05), and ventilatory index (from 1,445+/-148 to 794+/-139, P <0.05). Survival was 6/6 animals with PFC ventilation compared to 1/4 with conventional gas ventilation with no more pulmonary trauma (mean PCI 12.6+/-1.8 vs. 11.4+/-4.0%, P >0.05) for a longer mean ventilatory period in the PFC group. We conclude that the PFC liquid technique of ventilation can improve respiratory physiology when conventional gas ventilation alone is proving inefficient. There was no significant difference in pulmonary trauma at morphometrics between gas and partial liquid ventilation.