Male Wistar rats were given ethanol chronically (20-30% of the energy as ethanol) in a nutritionally sufficient regimen. Controls received lipid as isoenergetic substitute for ethanol. Treatment lasted for 2 or 8 weeks. Hepatic protein synthesis was measured in fasted rats during a 32 min. continuous infusion of 3H-valine. After 2 weeks of treatment accumulation of hepatic protein was observed in the ethanol group, but there was no change in hepatic protein synthesis or morphology. After 8 weeks the rate of hepatic protein synthesis was decreased by 35% in the ethanol group, but there was no accumulation of protein and a slight accumulation of intracellular lipid droplets. Neither the subcellular distribution of incorporated 3H-valine, nor the activities and distributions of alcohol dehydrogenase and NADPH cytochrome c reductase were changed. Mitochrondrial cytochrome c oxidase activity was decreased in the ethanol group, and cytosolic and microsomal fractions showed higher cytochrome c oxidase activity in this group. Chronic ethanol treatment for 8 weeks had an adverse effect on general protein synthesis as well as on a specific enzyme in the liver in the absence of serious morphologic abnormalities.