The ARDSNet trial revealed that the use of a smaller tidal volume (VT) reduced mortality by 22%. However, three earlier studies that lowered VT did not find a decrease in mortality. We tested the hypothesis that the increased respiratory rate used in the ARDSNet lower VT strategy might have led to intrinsic positive end-expiratory pressure (PEEP(i)), raising total PEEP (PEEP(total)). Ten patients with acute respiratory distress syndrome (ARDS) were ventilated using the ARDSNet lower VT protocol. Respiratory rate was then reduced (10-15 breaths/minute) to obtain a VT of 12 ml/kg (ARDSNet traditional VT). PEEP on the ventilator (PEEP(nominal): 10.1 +/- 0.7 cm H2O), FIO2 (0.7 +/- 0.1), and minute ventilation (VE: 12.4 +/- 1.7 L/minute) were set using the ARDSNet protocol and maintained constant during the two ventilatory strategies. Values of airway pressure at end-expiration of a regular breath (PEEP(external)) and 3-5 seconds after the onset of an end-expiratory occlusion (PEEP(total)) were measured. PEEP(i) was calculated by subtracting PEEP(external) from PEEP(total). PEEP(total) and PEEP(i) were, respectively, 16.3 +/- 2.9 and 5.8 +/- 3.0 cm H2O during the lower VT strategy and 11.7 +/- 0.9 and 1.4 +/- 1.0 cm H2O during the traditional VT strategy (p < 0.01). The reduced mortality observed with the ARDSNet strategy may have been due to the protective effect of a higher PEEP(total).