The multiple inert-gas elimination technique (MIGET) is a complex mathematical model and experimental technique for understanding pulmonary gas exchange. Simpler mathematical models have been proposed that have a limited view compared with MIGET but may be applicable for use in clinical practice. This study examined the use of a simple model of gas exchange to describe MIGET retention and excretion data in seven pigs before and following lung damage caused by oleic acid infusion and subsequently at different levels of positive end-expiratory pressure. The simple model was found to give, on average, a good description of MIGET data, as evaluated by a chi(2) test on the weighted residual sum of squares resulting from the model fit (P > 0.2). Values of the simple model's parameters (dead-space volume, shunt, and the fraction of alveolar ventilation going to compartment 2) compared well with the similar MIGET parameters (dead-space volume, shunt, log of the standard deviation of the perfusion, log of the standard deveation of the ventilation), giving values of bias and standard deviation on the differences between dead-space volume and shunt of 0.002 +/- 0.002 liter and 7.3 +/- 2.1% (% of shunt value), respectively. Values of the fraction of alveolar ventilation going to compartment 2 correlated well with log of the standard deviation of the perfusion (r(2) = 0.86) and log of the standard deviation of the ventilation (r(2) = 0.92). These results indicate that this simple model provides a good description of lung pathology following oleic acid infusion. It remains to be seen whether physiologically valid values of the simple model parameters can be obtained from clinical experiments varying inspired oxygen fraction. If so, this may indicate a role for simple models in the clinical interpretation of gas exchange.