Busso, Thierry, and Peter A. Robbins. Evaluation of estimates of alveolar gas exchange by using a tidally ventilated nonhomogenous lung model. J. Appl. Physiol. 82(6): 1963-1971, 1997.The purpose of this study was to evaluate algorithms for estimating O₂ and CO₂ transfer at the pulmonary capillaries by use of a nine-compartment tidally ventilated lung model that incorporated inhomogeneities in ventilation-to-volume and ventilation-to-perfusion ratios. Breath-to-breath O₂ and CO₂ exchange at the capillary level and at the mouth were simulated by using realistic cyclical breathing patterns to drive the model, derived from 40-min recordings in six resting subjects. The SD of the breath-by-breath gas exchange at the mouth around the value at the pulmonary capillaries was 59.7 ± 25.5% for O₂ and 22.3 ± 10.4% for CO₂. Algorithms including corrections for changes in alveolar volume and for changes in alveolar gas composition improved the estimates of pulmonary exchange, reducing the SD to 20.8 ± 10.4% for O₂ and 15.2 ± 5.8% for CO₂. The remaining imprecision of the estimates arose almost entirely from using end-tidal measurements to estimate the breath-to-breath changes in end-expiratory alveolar gas concentration. The results led us to suggest an alternative method that does not use changes in end-tidal partial pressures as explicit estimates of the changes in alveolar gas concentration. The proposed method yielded significant improvements in estimation for the model data of this study.