Acetaldehyde, the toxic product of ethanol metabolism in the liver, covalently binds to a variety of proteins. Recent studies indicate that such binding can stimulate the production of antibodies against the acetaldehyde adducts. We raised rabbit antibodies which recognized various protein-acetaldehyde conjugates but not the corresponding control proteins. Such antibodies were used in immunohistochemical studies to find out whether acetaldehyde-generated epitopes can be detected from liver specimens of 13 human subjects with different degrees of alcohol consumption. While the specimens obtained from alcohol abusers (n = 4) and alcoholics (n = 3) exhibited marked positive staining for acetaldehyde adducts inside the hepatocytes in a granular uneven pattern, the control samples (n = 6) were almost devoid of immunoreactivity. In the alcohol abusers with an early stage of alcohol-induced liver damage, staining was detected exclusively around the central veins. The data indicate that intracellular acetaldehyde adducts occur in the centrilobular region of the liver of individuals consuming excessive amounts of alcohol. Immunohistochemical detection of such adducts may prove to be of value in the early identification of alcohol abuse and in elucidating the mechanisms of alcohol-induced organ damage.