Objective:To compare measurements of the effective pulmonary blood flow (&OV0422;ep, i.e., nonshunted fraction of cardiac output, &OV0422;t) by the inert gas rebreathing (RB) method and the thermodilution (TD) technique in critically ill patients.Design:Prospective, comparative study of a noninvasive method and an established invasive technique.Setting:An 11-bed general intensive care unit in a university hospital.Patients:A total of 14 critically ill patients, all mechanically ventilated and monitored with systemic and pulmonary artery catheters.Measurements and Main Results:&OV0422;epwas determined in duplicate by RB using a mass spectrometer for gas analysis. For each determination, &OV0422;twas measured in triplicate by the cold water bolus TD technique and averaged. Simultaneously mixed venous and arterial blood samples were analyzed to calculate the intrapulmonary shunt fraction and thereby convert estimates of &OV0422;tto &OV0422;ep. Mean difference between paired estimates (RB - TD) was 0.01 L/min, so for differences was 1.19 L/min, and 95% confidence interval for the bias was −0.45 to 0.47 L/min. Coefficients of variation for repeated &OV0422;epestimates were 8% (RB) and 12% (TD), respectively. Coefficients of variation for RB estimates of functional residual capacity and lung tissue volume were 6% and 17%, respectively.Conclusions:The RB method is a promising method for simultaneous noninvasive estimation of &OV0422;epand functional residual capacity in mechanically ventilated patients. However, further investigations are needed to evaluate potential problems of the method before it can be recommended for clinical purposes.