High levels of IgG antibodies to the multi-enzyme complex bovine pyruvate dehydrogenase (PDHC) were detected by a sensitive ELISA in all patients with histologically proven primary biliary cirrhosis (PBC), in a minority of patients with systemic sclerosis without overt PBC or with chronic liver diseases of another cause and in no rheumatoid arthritis or normal controls. Most (15/21) but not all of these positive patients recognized a 70-kD (E2) component of PDHC on immunoblotting. Additional recognition of a centromere-associated 140-kD polypeptide was associated with the presence of scleroderma-like features (Raynaud's phenomenon and sclerodactyly) in PBC, further emphasizing the serological and clinical overlap between these two conditions.