The main symptoms of ethanol intoxication, tolerance, and physical dependence presumably, derive from the effects of ethanol on the central nervous system. It is not known clearly how and to what extent these effects are caused by ethanol itself or by its metabolic derivatives, chiefly acetaldehyde, formed in the liver, and transported into the brain through the blood stream. Since the concentrations of acetaldehyde found in the blood and brain of human subjects and experimental animals are approximately 44 times lower than the lowest effective concentrations found in in vitro experiments, it remains to be established whether acetaldehyde derived under in vivo conditions from the oxidation of ethanol in the liver plays any significant role in suppressing the respiratory metabolism or other metabolic pathways in the brain. It is concluded that the site of ethanol effects on the central nervous system is probably associated with that part of the metabolic system that is dependent on normal functioning of the neuronal cell membrane and probably has little relation to the peripheral or central metabolism of ethanol.