Data are presented which suggest that the initial event involved in experimental autoimmune thyroiditis following injection of rabbits with homologous thyroglobulin in complete Freund's adjuvant is alteration of the thyroglobulin. Alteration of the thyroglobulin does not occur during incorporation into the adjuvant or in vitro storage in the adjuvant, and the mycobacteria in the adjuvant have no direct effect on the thyroglobulin. Most likely, the alteration results from an increase in hydrogen ion concentration within cells or local areas in the granuloma and the subsequent action of proteolytic enzymes. These conditions are probably established in the granuloma as the result of neutrophilic response to the mycobacteria in the adjuvant.
Rabbits injected with aqueous preparations of homologous thyroglobulin partially degraded in vitro with pepsin at acid pH produced antibody to native thyroglobulin and developed thyroiditis. Most of these rabbits responded to a subsequent injection of native thyroglobulin given 1 month later.