The arterial oxygen tension (PaO2) may increase when patients with the adult respiratory distress syndrome are turned from supine to prone. We sought to reproduce this observation in dogs with acute lung injury to study the physiologic mechanism by which the improvement in oxygenation might occur. Twenty anesthetized dogs were ventilated with a constant tidal volume (20 ml/kg) of 100% oxygen. Oleic acid (0.09 ml/kg) was injected into the right atrium while rotating the animals through 360 degrees in 4 stages. Animals in Group I (n = 5) remained supine for 10 to 120 min until the supine PaO2 fell below 200 mm Hg. Those in Group II (n = 4) were kept prone during this period. Dogs in Groups I and II were then turned supine or prone every 30 min 5 times. Cardiac output and pulmonary vascular pressures, functional residual capacity (helium dilution), and regional diaphragmatic motion (determined by dorsal and ventral diaphragmatic markers relative to markers on the chest wall seen on lateral chest radiographs taken at FRC and at end-inspiration) were obtained in each position. Eleven dogs were kept supine (Group III, n = 6) or prone (Group IV, n = 5) for 2 h after oleic acid infusion, after which intrapulmonary shunt (Qs/QT) and ventilation-perfusion heterogeneity were measured in the supine and prone positions using the multiple inert gas elimination technique.(ABSTRACT TRUNCATED AT 250 WORDS)