Twenty-eight patients developed severe, progressive acute respiratory insufficiency despite aggressive application of conventional respiratory therapy. Application of increased PEEP (18 torr or greater) resulted in a significant decrease in QA/QT. Selection of the optimal levle of PEEP for each patient required serial determinations of QA/QT and measurement of cardiovascular response. The overall survival rate was 61 percent. Acute respiratory insufficiency was a proximate cause of death in only one patient. Four of the patients (14 percent) developed a pneumothorax following institution of high PEEP therapy. Cardiac output was not affected adversely at any level of PEEP up to 32 torr (44 cm H2O). We conclude that high levels of PEEP can be therapeutic for patients with refractory respiratory failure when combined with intermittent mandatory ventilation and careful cardiovascular monitoring. As with any therapy, the optimum dose should be tailored to each patient according to his needs and response.