Although the presence of anti-mitochondrial antibodies is the main characteristic of primary biliary cirrhosis (PBC), other autoantibodies have been described in this disease. This study employs immunoblot methods to test whether the sera of PBC patients also contain antibodies directed against nicotinic acetylcholine receptors (AChR). We show that the majority of patients' sera indeed react with AChR just as sera of myasthenic patients do. In contrast, however, these anti-AChR antibodies do not lead to significant clinical symptoms of myasthenia. In all cases studied, PBC sera recognized a protein with the molecular weight of the alpha-chain of acetylcholine receptor (40 kDa). In addition, with both liver mitochondria and AChR-rich membranes as antigens, PBC sera reacted with proteins with apparent molecular weights around 68 kDa and the same pI values. This protein is not present in purified AChR preparations. These data suggest structural, if not functional, relationships between membrane components of liver mitochondria and muscle endplates.