The effect of graded increments in positive end-expiratory pressure (PEEP) on arterial oxygen partial pressure (PaO2) and shunt fraction (Qs/QT), oxygen delivery, and respiratory mechanics and work required to ventilate 8 critically ill patients is reported. The work required to ventilate the patients increases markedly with the application and progressive increase in the level of PEEP. However, improvement in lung mechanics lowers the net work of ventilating the lungs. At 20 cm H2O PEEP, the mean value for the work of ventilation in this group of patients is twice the mean value without PEEP. The increase in work of ventilation with PEEP is critical in the use of PEEP when patients are breathing spontaneously with or without intermittent mandatory ventilation.