The initiation of an autoimmune response requires the establishment of an appropriate microenvironment. This, in turn, involves several requirements, including antigen expression on the membrane surface of the target cells, class II antigen expression on the antigen-presenting cell or target cell, a relative systemic or local increase in the helper/inducer subset of T cells, and/or a relative decrease in the suppressor subset of T cells. All of these conditions have been described in the thyroid gland. Appropriate cellular interactions result in the appearance of activated T cells and the generation of cytotoxic T cells. The pathologic alterations may be produced by the local production of antibody and subsequent formation of immune complexes, by direct lymphocyte damage, or by lymphokine production. Autoimmune thyroid disease remains, to our minds, the most instructive paradigm of the organ-specific autoimmune endocrinopathies.