Antibodies generated against the nuclear constituents are known as antinuclear antibodies (ANA). This includes autoantibodies directed against the extractable (soluble in physiological buffers) nuclear antigen or ENA. The most prominent of ANAs/ENAs are autoantibodies which binds to ds-DNA, ss-DNA, histones, ribonucleoproteins (RNP) and the SS-A, SS-B, Sm antigens, Jo-1, and Scl-70. Two antibodies, anti-dsDNA and anti-Sm, appear to occur only in SLE. Others occur in a variety of autoimmune and mixed connective tissue diseases. A heterogeneous group of precipitating antibodies called anti-Jo-1 have been found in dermatopolymyuositis. Anti-Jo is present in approx. 25% of patients with myositis. Recently, Jo-1 has been demonstrated to be an RNA-associated 50kD polypeptide antigen. It has been identified as histidyl-tRNA-synthetase, the RNA being tRNA-his. The frequency of ANA-positives in various rheumatic diseases has been reported for SLE, rheumatoid arthritis (RA), progressive systemic sclerosis (PSS), polymyositis (PM), dermatomyositis (DM), mixed connective tissue diseases, drug-induced SLE, and Sjogren’s syndrome (SS). Most of these studies are based on tedious fluorescent ANA (FANA). Other techniques such as RIA, immunodiffusion, hemagglutination, electrophoresis and immunoblotting are also used to define antibody specificity. Recently, immunological assays (mostly ELISA) that determine the specificity of ANA have been used in studying patients with systemic rheumatic diseases.