The effects of chronic, intermittent ethanol exposure on brain cytochrome c oxidase (CO) activity levels were studied in young (3- to 4-month-old) and aged (29- to 30-month-old) male Wistar rats. The rats were given highly intoxicating doses of ethanol three times a day by intragastric intubation for four successive days, followed by a 3-day ethanol-withdrawal period. This 4-day ethanol-exposure with 3-day ethanol-withdrawal cycle was repeated five times to simulate the binge drinking of human alcoholics. The histochemical demonstration of CO showed a markedly decreased activity level in the medial prefrontal cortex (especially layer V pyramids and neuropil) of the ethanol-exposed rats of both age groups compared with findings for the respective controls. In the cerebellar vermis, CO activity level was decreased in the Purkinje neurons of the aged ethanol-exposed rats and in the granule cells of both young and aged ethanol-exposed rats. The CO activity level in the locus coeruleus was decreased in both young and old ethanol-exposed rats, but the decrease was more pronounced in the young ethanol-exposed group. Aging per se did not markedly change CO histochemical findings in either prefrontal or cerebellar cortex, but CO activity levels were increased in the locus coeruleus. In summary, results of the current study support our conclusion that CO activity levels were decreased in the cerebral and cerebellar cortices as well as in the locus coeruleus-CNS regions known to be negatively affected by chronic ethanol exposure. Defective energy metabolism due to decreased CO activity levels might compromise neuronal energy stores and thereby contribute to ethanol-induced brain dysfunction and irreversible CNS degeneration.