Three patients with biopsy-proven primary biliary cirrhosis subsequently developed a multisystem disorder and serologic abnormalities consistent with systemic lupus erythematosus. In one patient, antimitochondrial antibody titers fell to undetectable levels after the development of the extrahepatic manifestations. No patient had been exposed to D-penicillamine or other drugs capable of inducing a lupus-like condition. These patients further emphasize the difficulties in disease classification and underline the systemic nature of chronic liver diseases such as primary biliary cirrhosis.