Five healthy rhesus monkeys were ventilated with intermittent mandatory ventilation and 20 torr positive end-expiratory pressure (PEEP) for 8 hours. PEEP was increased to 25 torr and the monkeys were ventilated for 4 more hours. Lactated Ringer's solution and human salt-poor albumin were used to expand plasma and extracellular fluid volume throughout the entire period of study. Homologous blood was administered to maintain hematocrit at control levels and maintenance fluids were infused to maintain transmural pulmonary capillary wedge pressure at 5 to 15 torr. Although cardiac output, mean aortic blood pressure, oxygen consumption, venous admixture, transmural pulmonary capillary wedge pressure, HCO3- and in-vivo base excess were not changed when intermittent mandatory ventilation was employed, cardiac output and blood pressure were significantly depressed by brief periods of controlled mechanical ventilation when alternated with intermittent mandatory ventilation. Sporadic increases in arterial-venous oxygen content difference occurred. Arterial carbon dioxide tension was elevated moderately, with a concomitant depression of arterial pH. No pneumothorax occurred. High PEEP was well tolerated with intermittent manditory ventilation, intravascular volume expansion, and careful cardiovascular monitoring.