Multisystem autoimmune diseases such as systemic lupus erythematosus (SLE), primary Sjögren's syndrome (SS), scleroderma and polymyositis are characterised by the presence of antinuclear antibodies (ANAs). Immunoblotting and cDNA cloning studies reveal that the autoantigens of the multisystem autoimmune diseases are important proteins involved in nucleic acid metabolism, including tRNA charging, intron splicing, DNA uncoiling, and RNA polymerase co-factors. Each specific syndrome associates with a restricted variety of ANAs, e.g. anti-La with primary SS, anti-Sm with SLE, anti-synthetase enzymes with myositis, anti-topoisomerase 1 (Scl 70) with scleroderma, and anti-centromere with CREST. Precise characterisation of an ANA provides valuable diagnostic and prognostic information, and should be performed when an ANA is detected.