Setting an appropriate positive end-expiratory pressure (PEEP) value is determined by respiratory mechanics, gas exchange and oxygen transport. As these variables may be optimal at different PEEP values, a unique PEEP value may not exist which satisfies both the demands of minimizing mechanical stress and optimizing oxygen transport. In 15 surfactant-deficient piglets, PEEP was increased progressively. Arterial oxygenation and functional residual capacity (FRC) increased, while specific compliance of the respiratory system decreased. Static compliance increased up to a threshold value of PEEP of 8 cm H2O, after which it decreased. This threshold PEEP did not coincide with the lower inflection point of the inspiratory limb of the pressure—volume (PV) loop. Oxygen transport did not correlate with respiratory mechanics or FRC. In the lavage model, the lower inflection point of the PV curve may reflect opening pressure rather than the pressure required to keep the recruited lung open. Recruitment takes place together with a change in the elastic properties of the already open parts of the lung. No single PEEP level is optimal for both oxygen transport and reduction of mechanical stress.