Like most autoimmune diseases of humans, chronic lymphocytic (Hashimoto's) thyroiditis results from the combination of a genetic predisposition and an environmental trigger. A body of clinical and epidemiologic evidence points to excessive ingestion of iodine as an environmental agent. In genetically determined thyroiditis in animals, iodine enrichment has been shown to increase the incidence and severity of disease. Its mechanism of action is still uncertain. Using a new animal model of autoimmune thyroiditis, the NOD.H2(h4) mouse, we have been able to show that iodine enhances disease in a dose-dependent manner. Immunochemical studies suggest that iodine incorporation in the thyroglobulin may augment the antigenicity of this molecule by increasing the affinity of its determinants for the T-cell receptor or the MHC-presenting molecule either altering antigen processing or by affecting antigen presentation.