The incidence of serum antibodies to human low-density lipoprotein, to oxidized low-density lipoprotein, and to ceroid extracted from human atheroma was assessed in 100 subjects using an adaptation of the enzyme-linked immunosorbent assay technique. Patients with chronic periaortitis, subclinical chronic periaortitis, and ischemic heart disease, and "elderly control" individuals were compared with young, healthy adults. Provided that precautions were taken to prevent oxidation of the low-density lipoprotein during the assay, antibodies were not found to native human low-density lipoprotein. Antibodies to oxidized low-density lipoprotein or ceroid, usually both, were detected in all 20 patients with clinical chronic periaortitis, in 17 of 20 patients with subclinical chronic periaortitis, in 12 of 20 patients with ischemic heart disease, and in 10 of 20 elderly control subjects. Binding inhibition studies showed cross-reactions between oxidized low-density lipoprotein and ceroid. Western blotting after sodium dodecyl sulfate polyacrylamide gel electrophoresis showed that in some patients with clinical chronic periaortitis, these antibodies were directed against breakdown products of apolipoprotein B that resulted from oxidation of low-density lipoprotein. Antibodies to oxidized low-density lipoprotein or ceroid were not detected in healthy young adults. These findings show that chronic periaortitis is accompanied by autoallergy to ceroid, which is probably at least partly composed of low-density lipoprotein oxidized within the human atherosclerotic plaque, and that a number of middle-aged and elderly people without chronic periaortitis also have such antibodies.