Many different autoantibodies which react with a variety of different nuclear and cytoplasmic antigens have been described. Detection of some these antibodies has been shown to be clinically useful in a number of different autoimmune diseases. For many years, the detection of most of the clinically relevant antibodies was done with by immunofluorescence on tissue substrates and human cultured cell lines. Within the past few years, a number of technical advances has now made it possible to convert to enzyme immunoassay. The paper reviews the clinically relevant antibodies and discusses the variety of new methods which are now available for ANA detection in diagnostic laboratories.