['To determine whether mechanical ventilation using high tidal volume is associated with nonpulmonary organ dysfunction that can be attenuated by dexamethasone.', 'Prospective randomized animal intervention study.', 'Animal care facility in a university hospital.', 'Sedated and tracheostomized male Sprague-Dawley rats.', 'Three groups of rats were ventilated with different strategies: tidal volume = 9 mL/kg, positive end-expiratory pressure = 8 cm H(2)O, control group (C); tidal volume = 35 mL/kg, positive end-expiratory pressure = 0 cm H(2)O, overventilated group (OV); and tidal volume = 35 mL/kg, positive end-expiratory pressure = 0 cm H(2)O, plus administration of 6 mg/kg dexamethasone intraperitoneally (OV + dexamethasone). All rats were ventilated for 75 mins with respiratory rate = 70 breaths/min, FIO(2) = 0.35, and plateau time = 0.', 'Mean arterial pressure and peak airway pressure were monitored. We measured arterial blood gases, aspartate aminotransferase, alanine aminotransferase, lactate, nitrates and nitrites, tumor necrosis factor-alpha, and interleukin-6 serum concentration. Lung slices were prepared for blind histologic examination. Heart tissue was analyzed for cyclooxygenase-1 and -2 expression (reverse transcription-polymerase chain reaction). Compared with the C group, the OV group showed hypotension; worsened gas exchange; increased aspartate aminotransferase, lactate, nitrates and nitrites, and interleukin-6 serum concentrations; and hyaline membrane formation in the lungs, as well as increased cyclooxygenase-1 and cyclooxygenase-2 expression in the heart. Dexamethasone prevented the pulmonary and cardiovascular injury and attenuated the increase in aspartate aminotransferase, nitrates and nitrites, interleukin-6, and cyclooxygenase-1 and cyclooxygenase-2 expression.'] Is ventilation-induced lung injury in rats associated with organ injury and systemic inflammation that is attenuated by dexamethasone?