Primary biliary cirrhosis (PBC) is a chronic cholestatic liver disease characterized by inflammatory destruction of the intrahepatic bile ducts. The differential diagnosis for PBC often includes autoimmune hepatitis (AIH). Both diseases can show prominent plasma cells and other overlapping histologic features. It is interesting that both diseases can involve elevated levels of serum immunoglobulins, with IgM elevations typical of PBC and IgG elevations typical of AIH. We investigated whether this difference could be useful histologically by immunostaining plasma cells in liver biopsy specimens for IgG and IgM. We examined 56 cases: 18 of PBC and 38 of AIH. In PBC, plasma cells in the portal tracts were predominantly IgM+, whereas in AIH, plasma cells were predominately IgG+ (P < .0001). Immunostaining for IgM and IgG can be helpful in differentiating PBC from AIH.