Cardiopulmonary resuscitation (CPR) may be followed by slow recovery of brain function. The possible role of bicarbonate therapy was assessed by analysis of arterial blood and cerebrospinal fluid (CSF) in 20 dogs during cardiac arrest and CPR. Samples were taken in the control period and every 5 minutes post-arrest of 20 minutes. Group I received no post-arrest CPR. Arterial pH fell from 7.37 to 7.31 (P less than 0.01) and CSF pH from 7.34 to 6.94 (P less than 0.001). Arterial pCO2 rose from 39 to 65 mm Hg (P less than 0.005) and CSF pCO2 increased from 47 to 123 (P less than 0.02). With CPR alone (group II) arterial pH decreased from 7.39 to 7.19 (P less than 0.005), while arterial pCO2 and CSF pH and pCO2 were undhanged. CPR with bicarbonate therapy (mEq = weight in kg times 0.43 times 1.1 mEq/min of arrest) given every 5 minutes (group III), resulted in a rise in arterial pH from 7.41 to 7.81 (P less than 0.02). Excess bicarbonate administration during CPR may result in a marked dissociation between arterial and CSF pH as a consequence of rapid CO2 diffusion across the blood-brain barrier. Large ampounts of NaHCO3 given during CPR may contribute to post-CPR cerebral depresssion.