It is being increasingly realized that modes of mechanical ventilation that result in end-inspiratory alveolar overstretching and/or repeated alveolar collapse and re-expansion disturb the normal fluid balance across the alveolocapillary membrane. The effects of this include disturbance of the integrity of the endothelium and epithelium and impairment of the surfactant system and are similar to those seen in acute respiratory distress syndrome (ARDS). There is now also evidence that these modes of mechanical ventilation may result in the translocation of bacteria from the lungs into the bloodstream and the release of inflammatory mediators from the lung tissue into the systemic circulation. It may thus be speculated that mechanical ventilation may contribute to the development of multiple organ failure (MOF). Therefore, during mechanical ventilation, alveolar overstretching and the repeated collapse and re-expansion of alveoli should be prevented by ventilation modes that open up the lung and keep the lung open and ventilate with the smallest possible pressure amplitude. For the future, monitoring techniques should be developed that can evaluate, on-line, whether or not these therapeutic directives are being achieved.