Objective:To evaluate a model describing postoperative hypoxemia after cardiac surgery by using two variables, i.e., shunt and resistance to oxygen diffusion (Rdiff).Design:Estimation of these two variables in normal subjects and postoperative cardiac patients.Setting:The pulmonary function laboratory for the normal subjects and the intensive care unit for the cardiac patients.Patients/Subjects:Nine postoperative cardiac patients and six healthy subjects.Interventions:Inspired oxygen fraction was varied in normal subjects and in cardiac patients 3-6 hrs after surgery. This variation occurred in four to seven steps to achieve arterial oxygen saturations in the range 0.90-1.00.Measurements and Main Results:Measurements were taken of arterial oxygen saturation, cardiac output, ventilation, and end-tidal gases at each inspired oxygen fraction. These measurements gave the following estimates for the normal subjects: shunt = 3.9 ± 5.4% (mean ± SD) and Rdiff= −5 ± 16 torr/(L/min) [−0.7 ± 2.2 kPa/(L/min)]; for the cardiac patients: shunt = 7.7 ± 1.8% and Rdiff= 212 ± 230 torr/(L/min) [28.2 ± 30.6 kPa/(L/min)]. The increase in Rdiff(p= .01) was sufficient to explain the observed hypoxemia in these patients. The value for shunt was not significantly increased in the patients (p= .09). The two-variable model (shunt and Rdiff) gave a better prediction of arterial oxygen saturation than a model with shunt as the only variable (p= .02).Conclusions:In cardiac patients requiring supplementary oxygen, the respiratory abnormality could, in our model, be best described by an increased Rdiff, not by an increased shunt value.