Purpose: To study the effect of two tidal volumes on gas exchange, lung mechanics, and hemodynamics in 12 patients with acute respiratory distress syndrome (ARDS) within the first 72 hours of mechanical ventilation. Methods: Tidal volume (VT) was increased by 40% from the initial value at fixed positive end-expiratory pressure (PEEP) and matched minute ventilation by adjusting the respiratory rate (RR) of the ventilator. Initial VT and RR were 592 ± 42 mL and 19 ± 1 min-1, respectively. High VT amounted to 825 ± 54 mL with a RR of 12 ± min-1. Results: We found that at high VT (1) the index of oxygenation increased from 0.22 ± 0.03 to 0.32 ± 0.04 (P < .001) with a parallel decrease in the right to left venous admixture from 0.26 ± 0.02 to 0.23 ± 0.02 (P < .001), and in the ratio of physiological dead space to tidal volume (Vds/Vt) from 0.53 ± 0.05 to 0.46 ± 0.04 (P < .01), without impairment to hemodynamics and (2) respiratory system compliance improved significantly from 34.8 ± 2.8 mL/cm H2O to 37.2 ± 2.9 mL/cm H2O (P < .05). In 4 patients, we performed pressure-volume curves on PEEP with the ventilator finding an upward concavity reflecting progressive alveolar recruitment with increasing inflation volume in 3. Conclusions: High-tidal ventilation in the early stage of ARDS improved gas exchange, suggesting recruitment during the inspiratory phase. However, the benefit of better oxygenation should be weighed against the potential risk of barotrauma induced at high Vt. © 1994.