Trihydroxymethylaminomethane is described as an organic carbon dioxide buffer because an aqueous solution of it can maintain a virtually constant partial pressure of carbon dioxide in a gas phase in contact with the solution. Administered to hypercapnic and acidotic dogs it elevated the pH and decreased the pCO2of the serum while increasing the totol serum carbon dioxide content. Administered to three dyspneic, cyanotic, and stuporous or comatose patients, it aided in correcting the respiratory acidosis and hypercapnia in two patients, and in these the relief was followed by complete clinical recovery. In the third patient the dosage used was ineffectual but free from demonstrable sideeffects. These results can be explained by the assumption that trihydroxymethylaminomethane in vivo, as in vitro, reduces the pCO2of arterial blood and so reduces the severity of symptoms in patients with persistent hypercapnia.