Experimental autoimmunity was produced in rabbits following injection of altered homologous thyroglobulin. The thyroglobulin was altered by coupling to chemically defined haptens and by heating. With some preparations antibody to native thyroglobulin as well as thyroid lesions were produced. Injections of thyroglobulin coupled to the diazonium derivatives of arsanilic acid and sulfanilic acid were effective when given in either soluble form or incorporated into incomplete Freund's adjuvant) while injections of the same preparations precipitated by alum had relatively little effect on production of antibody or induction of lesions. The injection of native thyroglobulin in soluble form, incorporated into incomplete adjuvant or precipitated by alum usually resulted in production of little or no antibody and only rarely in the formation of lesions. The injection of a heterologous thyroglobulin into rabbits resulted in the production of antibody reacting with both the heterologous and rabbit thyroglobulin, but no thyroid lesions were observed.