The authors evaluated the accuracy of a system to measure respiratory gas exchange on an on-line basis by comparing it with a gas collection method. The system incorporates a hot-wire flowmeter, a mass spectrometer, and a microcomputer. It performs on-line compensation for both transport delay and dynamic response of the mass spectrometer. Compensation of flow measurement for changing gas fractions also is performed. Excellent linear correlations were obtained between the two methods: 1) in animals during mechanical ventilation with room air (&OV0312;O2: r = 0.995; &OV0312;CO2: r = 0.993), and nitrous oxide in oxygen (&OV0312;O2: r = 0.975; &OV0312;CO2: r = 0.976); and 2) in men spontaneously breathing room air at different workloads (&OV0312;O2: r = 0.999; &OV0312;CO2: r = 0.998), and higher inspired oxygen fractions (FlO20.38 to 0.75) (&OV0312;O2: r = 0.910; &OV0312;CO2: r = 0.988). The authors consider that the system is suited for accurate and continuous measurement of respiratory gas exchange during mechanical ventilation, anesthesia, and exercise testing.