Objective. To evaluate a computer-based, real-time, multibreath nitrogen washout technique in mechanically ventilated patients, incorporating an in-line flow measurement device to measure functional residual capacity and two indices of gas mixing, ventilatory efficiency, and alveolar mixing efficiency. Setting: ICU, Charing Cross Hospital, London. Design: Within-patient reproducibility of a multibreath nitrogen washout technique. Patients. Seven intubated patients requiring mechanical ventilation. One patient completed two sets of readings. Interventions. Patients were connected to a pneumatically driven ventilator fitted with a switching device to be operated either by an appropriate oxygen-nitrogen mixture or equivalently blended oxygen-argon mixture. An inspiratory-expiratory, two-way valve was attached to the delivery port of the ventilator, with a pneumotachograph for flow measurement and a gas sampling probe for gas concentration measurement in line with the patient's endotracheal tube. The analog signals were digitized and handled by a microcomputer. Measurements and Main Results: No significant differences were found for any index, with coefficients of variation of 1.5%, 2.9%, and 2.1% for functional residual capacity, ventilatory efficiency, and alveolar mixing efficiency, respectively. Conclusions. This method gives excellent reproducibility for biological measurements in a clinical setting and shows that these measurements can readily be made on mechanically ventilated patients.