We have attempted to simplify the breath-holding method for measuring mixed venous PCO2 by the use of a single breath of 100% O2. This method is based on analysis of partial pressures of CO2 in three samples of alveolar gas obtained at 5, 10, and 15 sec of breath-holding after inspiration of 100% oxygen. Assuming exponential build-up of CO2 in alveolar gas, oxygenated mixed venous PCO2 can then be determined. Results in 35 subjects were compared with those of the previously reported breath-holding method for estimating oxygenated mixed venous PCO2 based on inspiring two gas mixtures; correlation coefficient was found to be 0.92. In 17 patients, samples of blood were obtained from the pulmonary artery by percutaneous catheterization; measured values in blood correlated well with the oxygenated non-invasively determined values (r = 0.83).