Chronic ethanol ingestion has been suggested to trigger the formation of antibodies that recognize acetaldehyde-protein condensates. In this study, assays for immunoglobulin (Ig) A, IgG, and IgM antibodies to acetaldehyde-derived adducts were performed on sera of 140 alcohol consumers, 19 patients with nonalcoholic liver disease (NALD), 35 healthy nondrinking controls, and 10 nondrinking patients with IgA or IgG myeloma. Anti-acetaldehyde (Ach)-adduct antibodies of each Ig isotype were found from the alcohol abusers. In alcoholic liver disease (ALD, n = 86) IgA titers were elevated in 69% of the patients. These titers were significantly higher than those from patients with NALD (P < .001), nondrinking controls (P < .001), or heavy drinkers (n = 54) without any clinical and biochemical signs of liver disease (P < .001). In contrast, anti-adduct IgG titers were significantly elevated both in ALD and in heavy drinkers as compared with patients with NALD (P < .001) or nondrinking controls (P < .01 and P < .05, respectively). The anti-adduct immunoglobulin (Ig)A, IgG, and IgM titers in patients with alcoholic liver disease (ALD) correlated with the combined clinical and laboratory index of liver disease severity (rs = .497, P < .001; rs = .361, P < .01; and r(s) = .322, P < .01). Anti-adduct IgA titers also correlated with serum bilirubin (r = .768, P < .001) and interleukin 6 (r = .504, P < .001). Anti-adduct IgG titers were, in turn, found to correlate with the presence of inflammation (P < .01) and necrosis (P < .01). During follow-up studies of individual patients, parallel changes were observed in the anti-adduct IgG titers, disease severity, and serum markers of fibrogenesis. The present results provide evidence that antibodies representing distinct Ig classes directed against acetaldehyde (Ach)-derived adducts of proteins are formed in alcoholic patients showing an association with the severity of liver disease. The follow-up data also support an association between such immune responses and the aggravation of liver disease.