Intact living frogs were equilibrated for 3/4-2 hrs. in gaseous mixtures containing varying amounts of CO2 in room air, in high and low O gaseous mixtures and in room air during simultaneous administration of NaCN in the dorsal lymph sac. At the end of the equilibration period, the frog brain was removed quickly, with due precaution to prevent gas exchange, and analysed for total CO2 by the Ba(OH)2 electrical conductivity method. The total CO2 content of the brain in a high O gaseous mixture, in room air, in a low O mixture and in room air during cyanide poisoning were 27.4, 22.8, 13.3 and 9.9 volumes % respectively. When CO2 was added to these mixtures the same relative positions of the curves held true. These results indicate an increased buffering capacity of the brain when oxidations are improved and a decreased buffering capacity when oxidations are impaired. Applying the Henderson-Hasselbalch equation it is computed that for a CO2 pressure of 25 mm. Hg the pH of the brain in the order of the conditions named would be approximately 7.33, 728, 7.19 and 7.10. Conversely, for a pH of 7.2 the CO2 pressure would be approximately 36, 33, 23 and 16 mm. Hg. It is, therefore, suggested that the decreased CO2 pressure and H-ion concentration of the blood commonly associated with temporarily impaired oxidations may be accompanied by an increased acidity of the brain. When the curves of these experiments are compared with CO2 dissociation curves of frog''s blood or of those of excised muscle and nerve obtained with other methods it appears that frog''s brain is better buffered than frog''s muscle or nerve but less well than frog''s blood. The significance of the relative buffering capacity of brain compared to that of blood, muscle and nerve is discussed.