Chronic hepatitis delta virus infection is associated with the presence of autoantibodies to rat forestomach and thymus in approximately 60% of patients' sera. We have characterized the antigen against which these autoantibodies are directed as a protein of 46 kD by immunoblotting studies on rat forestomach and thymus extracts. Normal human sera or sera from patients with other hepatic or non-hepatic autoimmune disorders did not bind to this protein. The immunoblot assay was more sensitive than immunofluorescence. Maximal titre was 1:10,000 versus 1:5120. By techniques of elution of specific antibodies from immunoblots, our results showed that the same antigen was present in both tissues. This antigen did not share common epitopes with hepatitis delta virus (HDV). Patients' sera depleted of basal cell layer and thymic stellate epithelial cell antibodies by absorption with the corresponding tissue extract maintained the HDV antibody titres. The autoimmune phenomena observed in patients with HDV infection seems to be a colateral process induced by the replication of delta virus in the host.