Antibodies against thymus epithelial cells (anti-TEC) and the basal cell layer (BCLA) of squamous epithelia have been described in association with HDV-related chronic liver disease (CLD). Data are lacking on their presence during nAnB virus infection. Sera from 51 patients with nAnB post-transfusion hepatitis, including acute and chronic cases diagnosed during a prospective study on candidates for cardiac surgery, and 167 with various forms of CLD were tested for the presence of anti-TEC and BCLA using indirect immunofluorescence on human thymus and rat forestomach sections. Both antibodies mainly occurred in nAnB, HDV and cryptogenic CLD (anti-TEC: 51%, 47% and 42%; BCLA: 29%, 38% and 31%, respectively). The prevalence of anti-TEC in nAnB CLD turned out to be higher than that recorded in alcoholic, HBV-related, autoimmune, liver and kidney microsomal antibody positive CLD and primary biliary cirrhosis (p ranging from less than 0.03 to less than 0.0004). Two monoclonal antibodies (Mabs) to cytokeratins gave a pattern superimposable on that of spontaneous anti-TEC (both Mabs) and BCLA (only one). Antibodies against epithelial constituents, presumably targeting cytokeratin-associated antigens, occur not only in HDV CLD, as previously reported, but also in nAnB CLD, where they might represent a diagnostic aid, due to the unavailability of reliable serological markers of nAnB infection. The close similarity of anti-TEC and BCLA status between nAnB and cryptogenic CLD suggests a nAnB etiology of at least a proportion of chronic liver patients at present scored as cryptogenic.