This study was performed in order to delineate the combined effects of protein deficiency and chronic ethanol ingestion on the rat pancreas. Rats fed ethanol in combination with protein-deficient diets developed marked steatosis, whereas alcohol ingestion with nutritionally adequate diets and protein deficiency alone each were associated with a more moderate degree of pancreatic lipid accumulation. On biochemical analysis, it was found that protein deficiency decreased pancreatic phospholipid content. Furthermore, both protein deficiency and chronic ethanol consumption increased pancreatic cholesteryl ester content, and their effects were additive. Functional changes were studied using isolated pancreative acini. Protein deficiency depressed the tissue content of lipase and the ability of pancreatic acini to secrete lipase. Chronic ethanol feeding increased lipase levels in the acini and also their secretory capacity. Thus, to the extent that enzyme accumulation in the pancreas plays a role in the pathogenesis of alcoholic pancreatitis, these results may explain the higher incidence of pancreatitis in well-nourished alcoholics that has been documented in dietary surveys.