BACKGROUND: The role of gravity in the redistribution of pulmonary blood flow during one-lung ventilation (OLV) has been questioned recently. To address this controversial but clinically important issue, we used an experimental approach that allowed us to differentiate the effects of gravity from the effects of hypoxic pulmonary vasoconstriction (HPV) on arterial oxygenation during OLV in patients scheduled for thoracic surgery. METHODS: Forty patients with chronic obstructive pulmonary disease scheduled for right lung tumour resection were randomized to undergo dependent (left) one-lung ventilation (D-OLV; n=20) or non-dependent (right) one-lung ventilation (ND-OLV; n=20) in the supine and left lateral positions. Partial pressure of arterial oxygen (PaO2) was measured as a surrogate for ventilation/perfusion matching. Patients were studied before surgery under closed chest conditions. RESULTS: When compared with bilateral lung ventilation, both D-OLV and ND-OLV caused a significant and equal decrease in PaO(2) in the supine position. However, D-OLV in the lateral position was associated with a higher PaO2 as compared with the supine position [274.2 (77.6) vs. 181.9 (68.3) mmHg, P<0.01, analysis of variance (ANOVA)]. In contrast, in patients undergoing ND-OLV, PaO2 was always lower in the lateral as compared with the supine position [105.3 (63.2) vs. 187 (63.1) mmHg, P<0.01, ANOVA]. CONCLUSION: The relative position of the ventilated vs. the non-ventilated lung markedly affects arterial oxygenation during OLV. These data suggest that gravity affects ventilation-perfusion matching independent of HPV.