1. Serum samples from patients with alcoholic heart muscle disease and from control subjects with and without heart disease who did not drink to excess were screened by Western immunoblotting for antibodies to acetaldehyde-modified cardiac cytosolic proteins. 2. Two of the 64 control samples (from subjects with and without heart disease who were not drinking and from subjects with alcoholic liver disease) had detectable (IgG) antibody to acetaldehyde-modified cardiac proteins. 3. By contrast, 7 of 21 (33%) patients with alcoholic heart muscle disease had antibodies against cyanoborohydride-stabilized, acetaldehyde-modified human cardiac cytosolic protein antigens (P < 0.001). 4. Antibodies were of IgG class in six patients and IgA class in five. The molecular sizes of the protein antigens observed ranged from 58 to 120 kDa. 5. These results suggest that a proportion of patients with alcoholic heart muscle disease develop immunogenic cardiac protein-acetaldehyde adducts. The presence of antibodies to these adducts may be a marker for the diagnosis of this heart disease, or possibly for its pathogenesis.