The use of continuous positive airway pressure (CPAP) and intermittent mandatory ventilation (IMV) in spontaneously breathing, intubated patients has prompted the development of new procedures for measuring functional residual capacity (FRC), The authors have developed a system for measuring FRC by the multiple breath nitrogen washout technique, which is suitable for use on intubated patients breathing with CPAP, IMV, or intermittent positive pressure ventilation (CONTROL) and on nonintubated patients. This system uses a pair of synchronized volume ventilators to permit a step change in inspired N2fraction while providing therapeutic ventilatory support. A rapid-response nitrogen analyzer and a modified bellows spirometer are used for continuous measurement of airway nitrogen concentration and expired gas flow rate. FRC is calculated on-line by a digital computer. The system accuracy was tested on a mechanical lung simulator in the CPAP and CONTROL modes. The measured volume was found to agree within 58 ± 52 ml of the actual volume in the CONTROL mode and within 104 ± 22 ml in the CPAP mode. The system was also tested for repeatability by making duplicate FRC determinations in patients with respiratory insufficiency. In the 18 patients studied, the correlation coefficient of these duplicate measurements wasr= 0.987 and the mean difference between measurements was 49 ± 24 ml. This noninvasive system also provides data used to calculate anatomical deadspace by Fowler's method (VSDS) and uniformity of ventilation (V/V) for multicompartment lung models.