In ten patients requiring respiratory support for an episode of acute respiratory failure (ARF), the best therapeutic level of PEEP was determined by measurement of changes in lung and chest wall compliance (CT) during a PEEP challenge from 0 to 20 cm H2O. During this challenge, hemodynamic monitoring combined with thermodilution measurement of right ventricular (RV) ejection fraction (EF) and two-dimensional echocardiographic measurement of RV size permitted assessment of the effects of increasing levels of PEEP on RV function. RV preload, as reflected by RV end-diastolic volume (EDV) and two-dimensional RV end-diastolic area (EDA), remained unchanged and RV diastolic compliance progressively decreased. On the other hand, RV systolic function, as assessed by RVEF and two-dimensional RV fractional area contraction (FAC), was progressively depressed. Substantial deleterious effects of PEEP were noted at high levels of PEEP including reduced CT and augmented pulmonary vascular resistance. Inadequate increase in RV preload to compensate for increased RV afterload resulted in depressed RV systolic function and contributed to the reduction in cardiac output. Finally, two-dimensional echocardiography proved to be more sensitive than fast-response thermodilution to evaluate change in RV function.