The goal of this study was to assess lung morphology in patients with acute lung injury according to the presence or the absence of a lower inflection point (LIP) on the lung pressure-volume (P-V) curve and to compare the effects of positive end-expiratory pressure (PEEP). Eight patients with and six without an LIP underwent a spiral thoracic CT scan performed at zero end-expiratory pressure (ZEEP) and at two levels of PEEP: PEEP1 = LIP + 2 cm H2O and PEEP2 = LIP + 7 cm H2O, or PEEP1 = 10 cm H2O and PEEP2 = 15 cm H2O in the absence of an LIP. The volumes of air and tissue within the lungs were measured from the gas-tissue ratio and the volumes of overdistended and normally, poorly, and nonaerated lung areas were determined by the analysis of the frequency histogram distribution. In the ZEEP condition, although total lung volume, volume of gas, and volume of tissue were similar in both groups, the percentage of normally aerated lung was lower (24 +/- 22% versus 55 +/- 12%, p < 0.05) and the percentage of poorly aerated lung was greater (40 +/- 12% versus 23 +/- 8%, p < 0.05) in patients with an LIP than in patients without an LIP. Lung density histograms of patients with an LIP showed a unimodal distribution with a peak at 7 Hounsfield units (HU). Lung density histograms of patients without an LIP had a bimodal distribution, with a first peak at -727 HU and a second peak at 27 HU. Total respiratory system and lung compliances were lower in patients with an LIP whereas all other cardiorespiratory parameters were similar in the two groups. In both groups, PEEP induced an alveolar recruitment that was associated with lung overdistension only in patients without an LIP. The amount of lung overdistension was related to the volume of lung parenchyma, characterized by a CT number less than -800 HU before PEEP implementation (y = 0.52x + 4, R = 0.87, and p < 0.0001). This study shows that the presence or the absence of an LIP on the lung P-V curve is associated with differences in lung morphology. In patients without an LIP on the lung P-V curve, normally aerated lung areas coexist with nonaerated lung areas and increasing levels of PEEP result in lung overdistension rather than in additional alveolar recruitment. In patients with an LIP, air and tissue are more homogeneously distributed within the lungs and increasing levels of PEEP result in additional alveolar recruitment without lung overdistention.