Recent evidence suggests that neonatal infection with Reovirus type 3 (Reo-3) may play an important role in the pathogenesis of certain idiopathic cholestatic liver diseases of children. Whether this virus is of pathogenetic importance in similar diseases seen in adults is unclear. In this study, sera from 22 adults with idiopathic cholestatic liver disease (16 primary biliary cirrhosis (PBC) and six primary sclerosing cholangitis (PSC] were tested for antibody to Reo-3 virus by a standard hemagglutination inhibition assay. The results were compared to antibody prevalence in ten adults with various other causes of chronic liver disease and 11 healthy volunteers. Although patients with idiopathic cholestatic liver disease had a high prevalence of anti Reo-3 antibodies (20/22, 91%), similar prevalence rates were found in the two control populations (7/10, 70% in chronic liver disease controls and 11/11, 100% in healthy volunteers). Moreover, the geometric mean titres of antibody to Reo-3 virus were similar in all study groups. While these results do not exclude a pathogenetic role for Reo-3 viral infection, they do imply that some genetic predisposition must exist if Reo-3 infection is truly of pathogenetic importance in idiopathic cholestatic liver disease of adults.