Right ventricular (RV) dysfunction may occur due to increased RV afterload and, hence, might also contribute to the decrease in cardiac output following institution of PEEP in patients with adult respiratory distress syndrome (ARDS). To test this hypothesis, the authors examined the influence of PEEP on local and global RV function in 12 anesthetized dogs with experimental ARDS (eARDS) induced by pulmonary microembolization with glass beads and oleic acid. Local RV function was analyzed in the RV inflow tract (RVIT) and RV outflow tract (RVOT) by assessing both diastolic segment length, systolic segment shortening, and segment work (sonomicrometry). Global RV contractility was quantified by measuring maximum rate of pressure rise (dRVP/dtmax) and maximum velocity of contractile element shortening (Vmax). In eARDS, despite a fivefold increase in pulmonary vascular resistance, there was no change in cardiac index (CI), global RV contractility, RVIT and RVOT work, and RVIT shortening, whereas RVOT shortening decreased from 12.4 to 7.4% (P< 0.01). Diastolic segment length increased in RVIT (P< 0.05) but not in RVOT. PEEP of 10 cmH2O did not alter global RV contractility, RVIT and RVOT shortening, and RVIT work but reduced RVOT work (-35%;P< 0.01) and CI (-11%;P< 0.001). Cardiac index further decreased during PEEP of 20 cmH2O (-38%;P< 0.001), while global RV contractility remained intact despite decreased RVIT and RVOT shortening (-32% and −69%;P< 0.05) and work (-26% and −59%;P< 0.01) in the presence of reduced fiber preload in both regions. From these findings, it was concluded that 1) the decreased CI during mechanical ventilation with PEEP at constant right ventricular end-diastolic pressure (RVEDP) is not caused by depressed global RV contractility in dogs with eARDS and a normal myocardium prior to insult. Decreased diastolic segment length and segment shortening during PEEP suggest that 2) PEEP reduces stroke volume by the Starling mechanism rather than by ischemia of the RV free wall. Finally, regionally incongruent changes of fiber preload indicate that 3) local differences in RV wall compliance are likely to occur subsequent to eARDS and PEEP.