To investigate the cardiopulmonary effects of positive end-expiratory pressure (PEEP), values of 10, 20, and 30 cm of H2O, were applied to anesthetized, dorsally recumbent, ventilated ponies. After IV induction of general anesthesia, PEEP was superimposed on controlled ventilation with 100% oxygen, and changes in gas exchange and cardiac function were measured. Increasing values of PEEP in these ponies caused a linear increase in the mean (+/- SEM) functional residual capacity, from a control value (zero end-expiratory pressure) of 1.7 +/- 0.24 L to 2.2 +/- 0.31, 2.9 +/- 0.32 and 3.4 +/- 0.3 L at PEEP of 10, 20, and 30 cm of H2O, respectively (P less than 0.05). Paralleling these changes, intrapulmonary shunt fraction decreased significantly (P less than 0.05) from a control value of 12.9 +/- 0.5%, to 7.5 +/- 1.1 and 2.1 +/- 0.6%, at PEEP of 20 and 30 cm of H2O, respectively. Cardiac output was decreased by increasing values of PEEP, from control value of 11.7 +/- 1.56 L/min to 9.9 +/- 1.51, 8.8 +/- 1.33 and 5.62 +/- 0.56 L/min at PEEP of 10, 20, and 30 cm of H2O, respectively. Related to decreasing cardiac output, tissue oxygen delivery also decreased as PEEP was increased, from control value of 2.0 +/- 0.09 L/min to 1.8 +/- 0.07, 1.6 +/- 0.06, and 1.03 +/- 0.04 L/min at PEEP of 10, 20, and 30 cm of H2O, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)