The diffusion of gases brings the partial pressures of O2 and CO2 in blood and alveolar gas to an equilibrium at the pulmonary blood-gas barrier. Alveolar PCO2 (PACO2) dependson the balance between the amount of CO2 being added by pulmonary blood and the amount being eliminated by alveolar ventilation (V ̇ A). In steady-state conditions, CO2 output equals CO2 elimination, but during nonsteadystate conditions, phase issues and impaired tissue CO2 clearance make CO2 output less predictable. Lung heterogeneity creates regional differences in CO2 concentration, and sequential emptying raises the alveolar plateau and steepens the expired CO2 slope in expiratory capnograms. Lung areas that are ventilated but not perfused form part of the dead space. Alveolar dead space is potentially large in pulmonary embolism, COPD, and all forms of ARDS. When PEEP recruits collapsed lung units, resulting in improved oxygenation, alveolar dead space may decrease; however, when PEEP induces overdistention, alveolar dead space tends to increase. Measuring physiologic dead space and alveolar ejection volume at admission or examining the trend during mechanical ventilation might provide useful information on outcomes of critically ill patients with ARDS.