Primary biliary cirrhosis (PBC) has been classified as an autoimmune disease. It is characterized by a multitude of immune-mediated symptoms and phenomena. Humoral autoimmunity directed against mitochondrial auto-antigens or structures cross-reactive with these proteins represents the basis of one of the most specific tests in any autoimmune disease: the detection of auto-antibodies against pyruvate dehydrogenase. The molecular cloning and expression of antigens of the ketoacid dehydrogenase complex has led to the establishment of highly specific and reliable testing systems for anti-mitochondrial antibodies (AMA). The characterization of specific antinuclear auto-antibodies has contributed to the diagnosis of AMA-negative PBC and is an important marker in overlap syndromes of PBC and other autoimmune liver diseases.