PEEP improves the gas-exchange abnormalities that accompany adult respiratory distress syndrome (ARDS). However, since PEEP decreases cardiac output, it may also alter regional blood flow and therefore, substrate delivery to specific organs. To test this hypothesis, radiolabeled 15-mu microspheres were used to directly quantify the effects of mechanical ventilation with PEEP on regional blood flow to individual organs in animals. Mechanical ventilation alone produced a -21.2 +/- 3.6% and a -28.1 +/- 5.2% decrease in cardiac output at 30 and 60 min, respectively. The addition of 14 cm H2O PEEP resulted in little further reduction in cardiac output at 30 and 60 min (-28 +/- 2.3% and -36.4 +/- 4.9%, respectively). However, 25 cm H2O PEEP reduced markedly (p less than .01) cardiac output (-59.2 +/- 6.1% at 30 min and -55.1 +/- 4.0% at 60 min). Although blood flows to the kidney and brain were maintained, decreases in cardiac output were invariably accompanied by proportional decreases in blood flow to the heart. Intravascular volume expansion with saline (20 ml/kg) during 14 cm H2O PEEP significantly improved cardiac output (3.23 +/- 0.34 to 4.22 +/- 0.13 L/min; p less than .01) and proportionately increased blood flow to several regional vascular beds, including the heart. These data suggest that PEEP decreases cardiac output to produce reversible alterations in blood flow to a number of regional vascular beds. These PEEP-induced alterations in regional blood flow may have important implications for the development of multiple-organ failure in ARDS patients.