One-lung ventilation-related hypoxaemia (OLV-RH) can occur in patients with healthy lungs. In this case, PEEP frequently improves oxygenation. The aim of this study was to determine, in a healthy lung model of OLV, whether the increase in PEEP improved oxygenation and whether the mechanisms involved include both inspiratory lung recruitment and an end-expiratory lung volume increase. Since inhaled nitric oxide (iNO) may have a synergistic effect on oxygenation in the case of PEEP-induced recruitment, their association was also tested. Twenty pigs were studied during open-chest, left OLV. Arterial blood gases and haemodynamic variables were measured at different levels of PEEP (0, 5, 10 and 15 cm H2O) applied in random order with or without iNO 4 p.p.m. Pressure–volume curves were measured at each level of PEEP. PEEP5 and PEEP10 improved P a O 2 / F I O 2 ratio (P<0.005) and shunt (P<0.005) regardless of the presence of iNO. PEEP15 improved oxygenation and shunt only when it was associated with iNO (P<0.001). Whereas PEEP5, PEEP10 and PEEP15 were associated with a significant increase in end-expiratory volume (P<0.001), only PEEP5 and PEEP10 were associated with continuous lung volume recruitment (P<0.01). Moreover, PEEP15 induced a significant decrease in linear compliance (P<0.001). In a healthy porcine lung model of OLV-RH, moderate PEEP can improve oxygenation. This effect implies both expiratory and inspiratory pulmonary recruitment. Co-administration of 4 p.p.m. iNO was ineffective.