We have previously published a mathematical model of oxygen transport. Using several physiological assumptions, the model provides a non-invasive estimate of intrapulmonary shunt. During a larger study of lung injury in a pig model, we had the opportunity to check the validity of our assumptions and the accuracy of the model's predictions. We used six female pigs, average weight 12.8 kg. Following general anesthesia, tracheostomy and insertion of pulmonary venous and arterial lines, lung injury was induced by repeated saline lung lavage. Using hemodynamic measurements made at different levels of inspired oxygen, intrapulmonary shunt was calculated both by the traditional shunt equation and also by our mathematical model based on non-invasive measurements of FIO2 and SaO2. There was good agreement between the two methods of shunt calculation. Using linear regression the correlation coefficient was 0.95. Bland and Altman analysis showed a bias of -0.8 and precision of 12%. In a controlled setting, intrapulmonary shunt can be estimated from non-invasive measurements to a reasonable degree of accuracy. However, the calculation requires too many assumptions to be of general clinical value. The equations used provide a validated physiological model that acts as a useful tool for teaching cardiorespiratory physiology.