Circulating autoantibodies are often observed in liver disorders, especially in those thought to have an autoimmune etiology-such as primary biliary cirrhosis (PBC) and chronic active hepatitis (CAH). The pathophysiologic role of these antibodies, however, remains obscure. The present study was performed to evaluate the incidence and diagnostic value of different antinuclear antibodies in chronic liver diseases, and to assess whether the antibodies are a non-specific expression of the hypergammaglobulinemia observed in these disorders. We measured six different antinuclear and closely related antibodies (against ssDNA, dsDNA, Poly (I), Poly (dT), RNA and cardiolipin) and their IgG, IgA and IgM isotypes in the sera of 86 patients with autoimmune, as well as other chronic liver diseases--namely, PBC, CAH, alcoholic (AC) and cryptogenic cirrhosis (CC). Antibodies against all the various nuclear antigens were detected in all diseases studied. The incidence ranged from 4% (anti-cardiolipin-IgG in CC) to 74% (anti-Poly (dT)-IgM in PBC). Although the antibody profiles differed among the various disease entities, they were not distinct enough to be of any clinical diagnostic value. In alcoholic cirrhosis antibody levels correlated with corresponding immunoglobulin isotype levels (notably IgA), suggesting a non-specific expression of hypergammaglobulinemia. In the other liver diseases such a correlation was lacking, favoring the existence of an underlying specific antigenic stimulation, or some other more specific immune dysfunction.