Several recent reports have shown that antibodies reactive with acetaldehyde (AcH)-modified epitopes are present in alcoholics. However, similar antibodies have also been found in patients with non-alcoholic liver disease and control subjects. In each of these studies total immunoglobulin binding to the AcH-modified proteins was measured, with no attempt being made to identify the classes of immunoglobulin involved. In the present study we employed an enzyme-linked immunosorbent assay (ELISA) to assess the classes of immunoglobulin involved in this response, using plasma samples from 97 alcoholics with varying degrees of liver disease, 35 patients with non-alcoholic liver disease and 33 control subjects. All three groups exhibited a large IgM response and a negligible IgG response. However, the alcoholics exhibited a significantly higher IgA response than either of the other groups. This suggests that the measurement of the IgA response to AcH-modified epitopes may be a specific marker of ethanol abuse.