We have developed a model of oral ethanol ingestion in the ferret by providing a complete liquid diet in which 21% of the total caloric intake is given as ethanol. After 3 weeks of ethanol treatment, migration inhibitory factor activity from ferret lymphocytes was significantly decreased when compared to animals fed a dextrose-substituted, identical liquid diet. Lymphocyte blastogenesis in response to the mitogen, phytohemagglutinin, was also decreased after 6 weeks of ethanol ingestion. Histopathologically, hepatic cell degeneration, fat deposition, and "Mallory body-like" material were present after 11 weeks of therapy. Bone marrow aspirate cells from the iliac crest of ethanol-fed animals showed vacuolization in both erythroid and myeloid elements after 6 weeks of ethanol ingestion. Mean ferret weights were not significantly different between the ethanol and dextrose control groups; serum ethanol and acetaldehyde concentrations were somewhat higher over the study period compared to those seen in human alcoholics. Therefore, we have designed a small animal model of the toxic effects of alcohol in which multiple organ systems exhibited evidence of ethanol-related disease.