The relationship between changes in cardiac output and intrapulmonary shunt associated with mechanical ventilation was evaluated in 20 patients with the adult respiratory distress syndrome (ARDS). The distribution of ventilation-perfusion (VA/Q) ratios and the level of intrapulmonary shunt was determined by the multiple inert gas technique. Pulmonary blood flow was distributed predominantly to either effective gas-exchanging units or shunt units. Positive end-expiratory pressure (PEEP) or high tidal volume ventilation led to decreases in shunt and cardiac output without altering the overall pattern of VA/Q distributions. Changes in shunt and cardiac output were quantitatively and qualitatively silimar and a strong correlation was found between changes in shunt and cardiac output with both PEEP and high tidal volumes (r = 0.76). Cardiac output depression associated with tese modes of ventilation appears to be a mechanism of shunt reduction in ARDS. Interpretation of improvements in gas exchange in ARDS must take into account concomitant hemodynamic changes.