Errors in measurement of exhaled gas volume, mixed expired oxygen and carbon dioxide concentrations, and inspired oxygen concentration and the presence of exhaled anesthetic agents cause errors in on-line calculated oxygen uptake that increase geometrically with increasing inspired oxygen concentration. No one has quantified the decrease in the magnitude of the error that might be realized if directly measured nitrogen concentration were included in the calculation. We used a computer model to evaluate this improvement, assuming an oxygen uptake of 200 ml/min and normal ventilatory parameters. Using a Monte Carlo technique, we generated 100 sets of data points, with random errors averaging 0.5% around the expected gas concentrations, and compared the accuracy of oxygen uptake calculated with and without inclusion of directly measured inspired and expired nitrogen concentrations. When the inspired oxygen fractions were 0.2, 0.5, and 0.8, the calculated oxygen uptakes ·% standard deviation were 200·4.3, 200·12, and 196·21 when directly measured nitrogen was includedversus200·3.5, 196·16, and 205·71 when it was not. The procedure was repeated, assuming 50 ml/min of anesthetic excretion and the calculated oxygen uptakes were 200·4.6, 202·12, and 195·17versus212·3.8, 251·17, and 398·64. Including direct measurement of inhaled and exhaled concentrations of nitrogen or another insoluble inert tracer gas allows accurate measurement of oxygen uptake, even in the presence of exhaled anesthetic gases. It also decreases the error in oxygen uptake determination by a factor of nearly six when the inhaled oxygen fraction is 0.8.