The effect of aerosolized perfluorocarbon (PFC) (FC77) on pulmonary gas exchange and lung mechanics was studied in a surfactant depleted piglet model. Sixty minutes after induction of lung injury by bronchoalveolar lavage, 20 piglets were randomized to receive aerosolized PFC (Aerosol-PFC, 10 ml/kg/h, n = 5), partial liquid ventilation (PLV) at FRC capacity volume (FRC-PLV, 30 ml/kg, n = 5) or low volume (LV-PLV, 10 ml/kg/h, n = 5), or intermittent mandatory ventilation (IMV) (Control, n = 5). After 2 h, perfluorocarbon application was stopped and IMV was continued for 6 h. Sixty minutes after the onset of therapy, PaO2 was significantly higher and PaCO2 was significantly lower in the Aerosol-PFC and the FRC-PLV groups than in the LV-PLV and the Control groups; p < 0.001. Six hours after treatment, maximum PaO2 was found in the Aerosol-PFC group: 406.4 +/- 26.9 mm Hg, FRC-PLV: 217.3 +/- 50.5 mm Hg, LV-PLV: 96.3 +/- 18.9 mm Hg, Control: 67.6 +/- 8.4 mm Hg; p < 0.001. PaCO2 was lowest in the Aerosol-PFC group: 24.2 +/- 1.7 mm Hg, FRC-PLV: 35.9 +/- 2.8 mm Hg, LV-PLV: 56.7 +/- 12.4 mm Hg, Control: 60.6 +/- 5.1 mm Hg; p < 0.01. Dynamic compliance (C20/c) was highest in the Aerosol-PFC group; p < 0.01. Aerosolized perfluorocarbon improved pulmonary gas exchange and lung mechanics as effectively as PLV did in surfactant-depleted piglets, and the improvement was sustained longer.