Changes in acidity of the circulating blood and of the cerebro-spinal fluid were studied in the dog to learn of the movement of acid and base between the tissues and the blood. The administration of CO2 and of Na2CO3 produced far greater changes in the acidity of the arterial blood than in the venous blood, indicating that the tissues acted as buffers to the blood. It is suggested that the buffering occurred primarily as a result of movement of CO2, for the injection of NaHCO3 produces approximately the same change in acidity in the arterial and venous blood. These conclusions are supported by a study of changes in acidity of the cerebro-spinal fluid. Administration of CO2 increased acidity of the cerebro-spinal fluid and increased ventilation; Na^Os produced the reverse effects. NaHCO3 increased the acidity of the fluid and increased ventilation. These results are explained by the relative impermeability of cell membrane to base and to the increase in CO2, H2CO3, HCO3, which are free to exert an acid effect beyond the blood. The results are in accord with the acid mechanism of respiratory control.