The metabolism of the brain was studied in normal, schizophrenic, paretic and senile subjects, and the effect of alcohol, paraldehyde and morphine was studied. Arterio-venous differences for oxygen, carbon dioxide, glucose and lactic acid were determined by means of internal jugular puncture. The observations support the following conclusions:1. The O2 arterio-venous difference of the brain in schizophrenics, both before and after insulin therapy, is normal.2. In general paresis the O2 arterio-venous difference of the brain shows a slight diminution of questionable significance.3. The O2 arterio-venous difference of the brain in patients with cerebral arteriosclerosis is normal, but their systemic circulation is somewhat slow. This would indicate a reduced brain metabolism.4. The O2 arterio-venous difference in chronic alcoholism tends to be higher than normal and is associated with an elevated arterial glucose level.5. Alcohol and morphine diminish the O2 arterio-venous difference of the brain.6. In therapeutic doses paraldehyde did not diminish the O2 arterio-venous difference of the brain of chronic alcoholic patients.