Autoimmunity is thought to be a defect in immunologic tolerance, resulting in the activation and expansion of self antigen-specific T and B lymphocyte clones and the production of circulating antibodies, and a myriad of cytokines and other inflammatory mediators. This hypothesis, which speculates on an aberrant response of the immune system to normal self antigens has exerced a powerful influence on clinical investigations and therapeutic researches. Although much information has accumulated, the mechanism of autoimmune disease remains poorly understood and little attention has been paid to the hypothesis that autoimmune diseases might be caused by a conventional immunological response against self antigens for which tolerance has never been established. Clinical practice would undoubtedly get a lot out of it, as well as new therapeutic measures.