The response of intravascular (PBV) and extravascular (EVLW) pulmonary fluid volumes to varying degrees of positive end-expiratory pressure (PEEP) was examined using double indicator techniques (thermal green dye) in six open-chest anesthetized dogs during the production of oleic acid (0.15 cc/kg)-induced pulmonary injury. Data were obtained at a control state, then 1.5 hr after the oleic acid was injected. Positive-end expiratory pressure (5, 10, 15, and 20 cm H2O) consistently reduced cardiac output prior to and after oleic acid edema was created, with greater reductions occurring with higher levels of PEEP. Increasing amounts of PEEP consistently produced greater reductions in PBV (with and without pulmonary edema), though without significant effect on EVLW. PBV declined from 6.0 +/- 2.4 to 4.0 +/- 1.0 ml/kg with 20 cm H2O of PEEP (P less than .01) in the control state and 4.4 +/- 2.1 to 2.9 +/0 0.9 ml/kg (P less than .01) after oleic acid administration. It is concluded that PEEP significantly reduced intravascular pulmonary fluid volumes along with cardiac output, without changing EVLW. While the effects of altered left ventricular geometry were not examined, the displacement of blood from the central to the peripheral circulation during PEEP must substantially contribute to reductions in systemic flow.