This study was designed to examine whether the oxygenation response in the prone position differs in magnitude depending on the level of positive end-expiratory pressure (PEEP) applied in the supine position, and whether cardiac output (CO) increases in the prone position. In seven supine dogs, acute lung injury was established by saline lavage (arterial oxygen tension (Pa,O2)/inspiratory oxygen fraction (FI,O2) 17.8+/-9.6 kPa (134+/-72 mmHg)), and inflection point (Pflex) of the respiratory system was measured (6.6+/-1.4 cmH2O). Pa,O2/FI,O2 and CO of the supine and prone positions were obtained under the application of low PEEP and then under optimal PEEP (2 cmH2O below and above Pflex, respectively). The net increase in Pa,O2/FI,O2 by prone positioning was greater at low PEEP (27.3+/-12.0 kPa (205+/-90 mmHg)) than at optimal PEEP (4.4+/-13.0 kPa (33+/-98 mmHg)) (p=0.006). CO decreased significantly with optimal PEEP in the supine position (2.4+/-0.5 versus 3.1+/-0.4 L x min(-1) at baseline, p<0.001), and increased to 3.4+/-0.6 and 3.6+/-0.7 L x min(-1) in the prone position at 5 min and 30 min, respectively (both p=0.018). When the dogs were turned supine at optimal PEEP, CO again decreased (2.4+/-0.5 L x min(-1), p<0.001). In conclusion, the prone position augmented the effect of relatively low positive end-expiratory pressure on oxygenation, and attenuated the haemodynamic impairment of relatively high positive end-expiratory pressure in a canine acute lung injury model.