OBJECTIVE: "Open the lung and keep it open" is increasingly accepted as a fundamental principle for mechanical ventilation. However, it is sometimes very difficult, or impossible, to recruit the diseased lung. We questioned whether one could facilitate recruitment by using a low dose of fluorocarbon in a model previously shown to be non-recruitable by conventional sustained inflation maneuvers. DESIGN AND SETTING: Experimental prospective study in a university laboratory. ANIMALS AND INTERVENTIONS: Nine saline-lavaged rabbits subjected to prolonged large tidal volume mechanical ventilation to establish significant lung injury were randomly allocated to two groups: control [High Frequency Oscillation (HFO) alone: n=4] or 1 ml/kg fluorocarbon (FC) treated (HFO/FC: n=5) for 2+1 h (experiment 1). An additional four similarly prepared animals were treated by single-lung instillation of 0.5 ml/kg dose of fluorocarbon and underwent serial computerized tomography scans at a series of predetermined step-wise pressure increase in both lungs (experiment 2). MEASUREMENTS AND RESULTS: In experiment 1 there was a very significant improvement in oxygenation in HFO/FC group (PaO(2) increased from 108 mmHg to 424+/-81 mmHg; P<0.05) while there was no significant change in the control group. In experiment 2 lung volumes were determined using three-dimensional reconstruction. The lung having fluorocarbon showed a 2.4-fold increase in lung volume at inflation pressure of 15 cmH(2)O compared to the lung without fluorocarbon. CONCLUSIONS: We propose that the low equilibrium surface tension and positive spreading coefficient of fluorocarbon facilitates lung recruitment by ungluing adherent surfaces in this model of lung injury.