Patients with chronic viral hepatitis commonly have immunologic manifestations, including autoantibodies and concurrent immune diseases. These immunologic findings may resemble those of autoimmune hepatitis and they are not disease specific. High titer autoantibodies (titers > or = 1:320) are uncommon in chronic viral hepatitis as are multiple concurrent autoantibodies. These findings reflect an autoimmune-predominant disorder in which the viral infection may be coincidental or facilitative. Concurrent immunologic disorders may be viral antigen-driven and associated with immune complex deposition (cryoglobulinemia, glomerulonephritis, cutaneous vasculitis, and polyarteritis) or autoantigen-driven (autoimmune thyroiditis and Sjögren's syndrome) and associated with host-rather than virus-specific factors. Genetic predispositions influence immunologic expression. Seropositivity for antinuclear antibodies is associated with HLA A1-B8-DR3, and concurrent immunologic diseases are associated with the DR4 allele. Interferon therapy is appropriate for patients with viral antigen-driven processes that depend on immune complex deposition and for patients with mild background autoimmune expressions. Corticosteroid therapy should be considered for those unusual patients with predominant autoantigen-driven processes since interferon treatment may exacerbate immune-mediated diseases. Patients with chronic hepatitis B and C can have similar immune features, but patients with chronic hepatitis C more commonly have autoantigen-driven processes.