A total of 18 patients with acute lung injury (ALI) were sequentially ventilated with two different modes of mechanical ventilation, each applied for a period of 24 h: (1) volume-controlled inverse ratio ventilation (VC-IRV), (2) airway pressure release ventilation (APRV). The individual sequence of both ventilatory modes was randomized. Ventilatory minute volume was adjusted for a PaCO2 of 35 to 45 mm Hg at the beginning of the study during the first ventilatory mode and then kept constant within preset limits. Hemodynamic variables were stable and similar during the 24-h periods of VC-IRV and APRV as well. Despite the lower sedation and spontaneous breathing during APRV, oxygen uptake was similar during both ventilatory modes. During the 24-h period of VC-IRV there was no relevant change of either airway pressures, alveolo-arterial O2 tension difference (AaDO2)/fraction of inspired oxygen (FIO2) or venous admixture. In contrast, peak airway pressures (Pawmax) during APRV were significantly lower (about 30%; p < 0.01), and decreased further within 24 h (p < 0.05). During APRV AaDO2/FIO2 and venous admixture improved significantly with time after more than 8 h (AaDO2/FIO2: 487 versus 414 mm Hg; p < 0.01; venous admixture: 20.6 versus 13.9%; p < 0.01; medians of onset versus end). The improvement was significantly different between both ventilatory modes (p < 0.01). We conclude that this indicates a progressive alveolar recruitment over time during ventilation with APRV.(ABSTRACT TRUNCATED AT 250 WORDS)