We studied 31 consecutive mechanically ventilated patients with acute respiratory failure in two stages: (1) During spontaneous breathing through the respirator, switching from full mechanical assistance to continuous positive airway pressure mode with 0 cm H2O pressure. We measured maximum inspiratory pressure and continuously monitored the pattern of breathing. After 8 to 25 min, none of the patients were able to sustain spontaneous breathing and mechanical ventilation was required to resume. (2) Subsequently, during mechanical ventilation, by manipulating the variables of the ventilator we simulated the pattern of spontaneous breathing the patients had just before the re-institution of mechanical ventilation. We assessed the respiratory mechanics by the constant flow end-inspiratory and end-expiratory occlusion method. Intrinsic positive end-expiratory pressure was present in 29 patients. The ratio of the mean inspiratory pressure per breath over the maximum inspiratory pressure (Pi/pimax), as well as Ppeak/pimax, had excessively high mean values, equal to 0.42 +/- 0.11 and 0.56 +/- 0.10, respectively. Pressure-time index was 0.14 +/- 0.04. When we plotted the Pi/Pimax and Ppeak/Pimax against the dynamic increase in FRC, we found that the Pi/Pimax of 13 patients (42%) and the Ppeak/Pimax of 25 of 31 patients (81%) were placed above a hypothetical critical line, representing the critical inspiratory pressures above which fatigue may occur. In addition, almost all patients were gathered around the critical line. We conclude that during discontinuation from mechanical ventilation (MV) almost all patients breathe against a high inspiratory load and their inspiratory muscles perform work that may lead to fatigue.