1. To study the validity of a CO2-rebreathing method at rest and during graded exercise, cardiac output was measured simultaneously on 59 occasions in 16 subjects with normal pulmonary function with the CO2-rebreathing method and the direct Fick method for oxygen. The correlation coefficient between the results of both methods was significantly higher during exercise than at rest.
2. No systematic difference was shown between (a-v̄)CO2 content difference determined on whole blood and end-tidal gas, which justified the exclusion of a correction factor for blood to alveolar gas Pco2 gradients.
3. In the calculation of cardiac output by the direct Fick method for CO2 and by CO2 rebreathing, a standard CO2 dissociation curve was preferred to a synthetic CO2 dissociation curve, constructed by allowance for changes in haemoglobin concentration, pH and oxygen saturation. The latter curve tended to increase values for cardiac output and induced a large dispersion around the line of identity, when compared with simultaneous cardiac output estimates by the direct Fick method for oxygen.