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Pleural effusion is a frequent finding in patients with acute respiratory distress syndrome. To assess the effects of pleural effusion in patients with acute lung injury on lung volume, respiratory mechanics, gas exchange, lung recruitability, and response to positive end-expiratory pressure.A total of 129 acute lung injury or acute respiratory distress syndrome patients, 68 analyzed retrospectively and 61 prospectively, studied at two University Hospitals.Whole-lung CT was performed during two breath-holding pressures (5 and 45 cm H2O). Two levels of positive end-expiratory pressure (5 and 15 cm H2O) were randomly applied.Pleural effusion volume was determined on each CT scan section; respiratory system mechanics, gas exchange, and hemodynamics were measured at 5 and 15 cm H2O positive end-expiratory pressure. In 60 patients, elastances of lung and chest wall were computed, and lung and chest wall displacements were estimated.Patients were divided into higher and lower pleural effusion groups according to the median value (287 mL). Patients with higher pleural effusion were older (62 ± 16 yr vs. 54 ± 17 yr, p < 0.01) with a lower minute ventilation (8.8 ± 2.2 L/min vs. 10.1 ± 2.9 L/min, p < 0.01) and respiratory rate (16 ± 5 bpm vs. 19 ± 6 bpm, p < 0.01) than those with lower pleural effusion. Both at 5 and 15 cm H2O of positive end-expiratory pressure PaO2/FIO2, respiratory system elastance, lung weight, normally aerated tissue, collapsed tissue, and lung and chest wall elastances were similar between the two groups. The thoracic cage expansion (405 ± 172 mL vs. 80 ± 87 mL, p < 0.0001, for higher pleural effusion group vs. lower pleural effusion group) was greater than the estimated lung compression (178 ± 124 mL vs. 23 ± 29 mL, p < 0.0001 for higher pleural effusion group vs. lower pleural effusion group, respectively).Pleural effusion in acute lung injury or acute respiratory distress syndrome patients is of modest entity and leads to a greater chest wall expansion than lung reduction, without affecting gas exchange or respiratory mechanics.