Summary The effect of acetaldehyde on the redox state of the nerve cell was investigated at 4 levels of organization: intact brain cortex in vivo , cortex slices, isolated nerve endings and the conventional subcellular fractions of the nerve cell. Aldehyde dehydrogenase activity was determined fluorometrically in the nuclear, mitochondrial, cytosolic and synaptosomal fractons from rat brain cortex. The activities for acetadehyde in these fractions were 0.331, 1.80, 0.219 a nd 0.759 nmole · mg protein −1 · min −1 , respectively. Two apparent Km values were observed in frozen and thawed mitochondrial preparations,1.0 × 10 −4 M and 1.3 × 10 −6 M. The higher value was probably due to the presence of intact mitochondrial membranes. The oxygen consumption of the synaptosomes was not sensitive to uncouplers but was inhibited by acetaldehyde (0.02–5m M ). The redox state was studied by measuring the NAD(P)H and flavoprotein fluorescence of brain mitochondria and synaptosomes. In these preparations the nicotinamide nucleotides were largely oxidized and the redox state was not affected by acetaldehyde. However, in cerebral cortex slices acetaldehyde caused a reduction of NAD(P) ** , detectible by measuring the surface fluorescence of the tissue slices at appropriate wavelengths. In vivo , acetaldehyde also caused reductionof NAD(P) in the cerebral cortex. The reduction could be demonstrated by measurements of the surface fluorescence of the cerebral cortex in vivo and by chemical measurements of the nicotinamide nucleotides in tissue samples obtained by the freeze-stop echnique.