Sera of 30 chronic alcoholic patients and 30 age-matched and gender-matched controls were examined for antibodies to brain tissues. We performed an indirect immunofluorescence assay using the patients' and controls' sera as first antibodies, and fluoresceinconjugated anti-human-immunoglobulin Ig-A, Ig-G and Ig-M as second antibodies, on frozen sections of normal human brain. Binding to neuronal cell nuclei of frontal cortex and septal area was found in 40% of patients, but only in 6.7% of controls. The antibodies belonged to the IgM, and additionally sometimes the IgA and IgG subclass. The relevance of these antibodies for the development of brain disease in chronic alcoholic patients is discussed.