Although the Fleisch pneumotachograph has many advantages, its flow-conductance characteristics are nonlinear and sensitive to changes in gas composition. The purpose of this study was to assess the effect of different O2, N2, and CO2 compositions on the nonlinearity of the Fleisch pneumotachograph flow-conductance characteristics, by use of a recently developed computerized calibration method. Hospital-grade O2 was mixed with room air to obtain seven gas mixtures (containing O2 percentages of 20.9, 28.3, 38.7, 52.8, 66.7, 78.7, and 99.6%). Within the accuracy of the applied method, the measured flow-conductance curves of the pneumotachograph had the same shape. Relative flow resistance of gas mixtures to room air was directly proportional to their O2 composition. Two O2-N2-CO2 mixtures were also tested. Their relative flow resistance compared with room air was proportional to the viscosity ratios. We concluded that the change in O2, N2, and CO2 composition does not affect the nonlinearity of the Fleisch pneumotachograph flow-conductance characteristics. However, the relative flow resistance compared with room air does change in a predictable way.