Identification of biochemical changes induced by ethanol ingestion would aid in the diagnosis and management of many alcohol-related problems in man. In this paper we identify a pH 5.5 alpha-mannosidase activity in the rat which is affected by chronic ethanol consumption. Chronic (16 wk) ingestion of alcohol (36% of calories) causes the activity of this alpha-mannosidase (thought to be the cytosolic alpha-mannosidase) in liver to decrease by 50%. We hypothesize that this deficiency of (pH 5.5) alpha-mannosidase activity may account for the reduced rate of secretion of glycoproteins by livers of alcohol-fed rats reported by other investigators (Volentine et al, Hepatology 1987;7:490-495).