This study was undertaken to characterize blood gas, pH, and lactate changes during and after cardiopulmonary resuscitation (CPR) in arterial and venous samples. Blood samples were withdrawn from the brachial artery, aortic arch, pulmonary artery, coronary sinus, and either the right or left cardiac ventricle of 24 anesthetized dogs. Ventricular fibrillation (VF) was induced electrically, and mechanical CPR was begun. Blood samples were withdrawn before CPR, at 2, 5, 7, and 9 minutes during CPR, and at 1, 3, 10, 30, and 60 minutes after defibrillation. Control arterial and venous samples indicated mild metabolic acidosis. During CPR, there was a significant arteriovenous difference in pH, PCO2, and PO2. With ventilation onset, arterial pH increased 0.25 units, PCO2 decreased 22 mm Hg, and PO2 increased 200 mm Hg. Venous blood gases exhibited gradual changes during the CPR period. With the re-establishment of circulation and spontaneous respirations, both the arterial and venous pH levels decreased to nearly 7.1, and PCO2 approached 40 mm Hg. Lactate increased to 32 mg/dl during 9 minutes of CPR and did not significantly differ after defibrillation. Blood gases and pH returned to control values within an hour. This study suggests that arterial blood gases are sensitive to rapid changes occurring in the pulmonary capillary bed, while venous blood gases reflect changes occurring in the systemic capillary bed.