We investigated the acid-base condition of arterial and mixed venous blood during cardiopulmonary resuscitation in 16 critically ill patients who had arterial and pulmonary arterial catheters in place at the time of cardiac arrest. During cardiopulmonary resuscitation, the arterial blood pH averaged 7.41, whereas the average mixed venous blood pH was 7.15 (P less than 0.001). The mean arterial partial pressure of carbon dioxide (PCO2) was 32 mm Hg, whereas the mixed venous PCO2 was 74 mm Hg (P less than 0.001). In a subgroup of 13 patients in whom blood gases were measured before, as well as during, cardiac arrest, arterial pH, PCO2, and bicarbonate were not significantly changed during arrest. However, mixed venous blood demonstrated striking decreases in pH (P less than 0.001) and increases in PCO2 (P less than 0.004). We conclude that mixed venous blood most accurately reflects the acid-base state during cardiopulmonary resuscitation, especially the rapid increase in PCO2. Arterial blood does not reflect the marked reduction in mixed venous (and therefore tissue) pH, and thus arterial blood gases may fail as appropriate guides for acid-base management in this emergency.