PEEP can significantly reduce cardiac output. This reduction in cardiac output is frequently attributed to transmission of airway pressure to intrathoracic vascular structures. We designed an acute lung injury (ALI) model in swine (n = 7) characterized by low lung thorax compliance (CLT) and compared the fractional trans-mission of airway pressure to pleura (PPL) and pericardium (PPc) and hemodynamics to normal animals (n = 5) during controlled mechanical ventilation (CMV) and PEEP. Fractional transmission of PEEP to PPL and PPc was reduced significantly from 62 ± 8% and 54 ± 19 (sn)% to 34 ± 7% and 36 ± 9% in normal and ALI animals, respectively. End-inspiration tracheal pressure was significantly higher in the low compliant group; thus, cardiac output was equally depressed in both groups despite reduction in fractional airway pressure transmission in ALI animals, possibly because absolute inspiratory PPL and PPc were similar due to increased pressure required to inflate injured lungs. The results of this investigation do not support the presumption that low CLT blunts hemodynamic consequences of CMV and PEEP.