The discovery of long acting thyroid stimulator in Graves' disease and autoantibodies specific for the thyroid in Hashimoto disease in 1956, were the earliest examples of autoimmune responses. Autoimmune thyroid disease has many important advantages in the investigation of autoimmune disease when compared to the other disease. It is possible to obtain thyroid tissue at biopsy and to investigate the histology by various methods and the interactions between thyrocytes and infiltrated mononuclear cells in vitro. Important autoantigens, such as the TSH receptor, thyroid peroxidase and thyroglobulin have already been cloned and each autoantigen has a specific function. Furthermore, we can observe precisely the clinical course of the disease using laboratory parameters. In this review, the pathogenesis of Graves' disease will be overviewed using the results obtained, mainly in our laboratory, in the following topics: (1) Immunogenetics: HLA class I and II, Gm, multiple genes (2) Trigger: bacteria, retrovirus (HIV, HTLV-I), radiation (3) Initiation and perpetuation of autoimmune responses: role of HLA class I and II antigens, characteristics of infiltrated mononuclear cells, interactions among thyrocytes, mononuclear cells and endothelial cells, role of cytokines, adhesion molecules (4) Autoantibodies: methods of determination and clinical correlates of TSH receptor antibodies (5) Autoantigens: structure and functional relationship of TSH receptor (6) Future studies: possible methods of treatment based on pathogenesis, a model of new treatment.