A high respiratory rate associated with the use of small tidal volumes, recommended for acute lung injury (ALI), shortens time for gas diffusion in the alveoli. This may decrease CO2 elimination. We hypothesized that a postinspiratory pause could enhance CO2 elimination and reduce PaCO2 by reducing dead space in ALI. In 15 mechanically ventilated patients with ALI and hypercapnia, a 20% postinspiratory pause (Tp20) was applied during a period of 30 min between two ventilation periods without postinspiratory pause (Tp0). Other parameters were kept unchanged. The single breath test for CO2 was recorded every 5 min to measure tidal CO2 elimination (VtCO(2)), airway dead space (V-Daw), and slope of the alveolar plateau. PaO2, PaCO2, and physiological and alveolar dead space (V-Dphys, V-Dalv) were determined at the end of each 30-min period. The postinspiratory pause, 0.7 +/- 0.2 s, induced on average < 0.5 cmH(2)O of intrinsic positive end-expiratory pressure (PEEP). During Tp20, VtCO(2) increased immediately by 28 +/- 10% (14 +/- 5 ml per breath compared with 11 +/- 4 for Tp0) and then decreased without reaching the initial value within 30 min. The addition of a postinspiratory pause significantly decreased V-Daw by 14% and V-Dphys by 11% with no change in V-Dalv. During Tp20, the slope of the alveolar plateau initially fell to 65 +/- 10% of baseline value and continued to decrease. Tp20 induced a 10 +/- 3% decrease in PaCO2 at 30 min (from 55 +/- 10 to 49 +/- 9 mmHg, P < 0.001) with no significant variation in PaO2. Postinspiratory pause has a significant influence on CO2 elimination when small tidal volumes are used during mechanical ventilation for ALI.