Li, M. H., J. Hildebrandt, and M. P. Hlastala.Quantitative analysis of transpleural flux in the isolated lung. J. Appl. Physiol. 82(2): 545–551, 1997.—In this study, the loss of inert gas through the pleura of an isolated ventilated and perfused rabbit lung was assessed theoretically and experimentally. A mathematical model was used to represent an ideal homogeneous lung placed within a box with gas flow (V˙box) surrounding the lung. The alveoli are assumed to be ventilated with room air (V˙a) and perfused at constant flow (Q˙) containing inert gases ( x) with various perfusate-air partition coefficients (λp, x ). The ratio of transpleural flux of gas (V˙pl x ) to its total delivery to the lung via pulmonary artery (V˙ v), representing fractional losses across the pleura, can be shown to depend on four dimensionless ratios: 1) λp, x , 2) the ratio of alveolar ventilation to perfusion (V˙a/Q˙), 3) the ratio of the pleural diffusing capacity (Dpl x ) to the conductance of the alveolar ventilation (Dpl x /V˙aβg, where βg is the capacitance coefficient of gas), and 4) the ratio of extrapleural (box) ventilation to alveolar ventilation (V˙box/V˙a). Experiments were performed in isolated perfused and ventilated rabbit lungs. The perfusate was a buffer solution containing six dissolved inert gases covering the entire 105-fold range of λp, x used in the multiple inert gas elimination technique. Steady-state inert gas concentrations were measured in the pulmonary arterial perfusate, pulmonary venous effluent, exhaled gas, and box effluent gas. The experimental data could be described satisfactorily by the single-compartment model. It is concluded that a simple theoretical model is a useful tool for predicting transpleural flux from isolated lung preparations, with known ventilation and perfusion, for inert gases within a wide range of λ.