We propose to study the mechanisms of altered gas exchange in Acute Respiratory Failure (ARF) utilizing the newly developed multiple inert gas technique, and to compare the data with more conventional techniques which utilize oxygen and carbon dioxide transfer. The mechanisms identified will be correlated with the apparent etiology and/or clinical setting, e.g., shock, aspiration, etc. We will assess the contribution of cardiac insufficiency to the marked hypoxemia of ARF by measuring mixed venous oxygen tension (PvO2) and cardiac output. We will evaluate the potentially deleterious effect of increasing shunt due to short term 100% oxygen breathing which is commonly used to measure right to left shunt. We will evaluate the effects of: 1) Stepwise increase in positive end expiratory pressure and 2) Stepwise increases in tidal volume on the distribution of ventilation/perfusion (VA/Q) and cardiac output. Utilization of the multiple inert gas technique for studying VA/Q will permit separation of low VA/Q units from right to left shunt and the separation of high VA/Q units from dead space. It does not require a change in inspired oxygen which itself may increase shunt. The application of this new technique while obtaining simultaneous data from standard techniques to a large number of patients with ARF should provide valuable information concerning the mechanisms of altered gas exchange. A critical evaluation of currently used empiric forms of shunt measurement and therapy--oxygen, PEEP, and increasing tidal volumes, each with inherent morbidity, should provide a more rational basis for therapy.