Previous studies demonstrated selective increases in mixed venous carbon dioxide tension (PvCO2) during CPR in a porcine model of cardiac arrest. This was associated with a decrease in end-tidal carbon dioxide concentration (ETCO2), possibly due to a critical reduction in cardiac output and therefore pulmonary blood flow during CPR. We investigated the relationship between ETco2 and cardiac output before cardiac arrest and during CPR. Observations in 19 minipigs confirmed a high linear correlation between ETco2 and cardiac output. We conclude that the increase in Pvco2 and the concurrent decrease in ETco2 reflect a critical reduction in cardiac output, which reduces alveolar blood flow to the extent that carbon dioxide clearance by the lung fails to keep pace with systemic CO2 production.