ABSTRACT— Spontaneous cell-mediated cytotoxicity (SCMC), antibody-dependent cellular cytotoxicity (ADCC) and proliferative lymphocyte stimulation in alcoholic liver disease (ALD) were investigated. Peripheral blood lymphocytes (PBL) from eight patients with advanced ALD and nine normal controls were tested against hepatoma cells (PLC/PRF/5) as targets. Target cells were grown in either normal culture medium or medium supplemented with 1 and 5% ethanol, respectively, for 24 to 48 h. Ethanol-exposed hepatoma cells exhibited profound and characteristic morphological alterations. Ethanol preincubation, however, proved to be without effect on immune reactions. Provided that hepatoma cells are an appropriate model, we assume that the proposed immune reactions in ALD are based on metabolic interactions operative only in vivo but do not parallel morphological alterations of liver cells directly induced by ethanol.