Publisher Summary This chapter discusses the autoantigens of the thyroid gland as well as the known proteins that seem to be characteristic of this organ. The important antigens can be understood on the basis of chemical analyses of their macromolecular nature. The properties of the autoantibodies and of the antoimmune disease related thyroid gland are also discussed. The thyroid antigens are a group of proteins that can be characterized as having either a soluble form or a membrane-attached form. From a physicochemical viewpoint, the soluble variety includes at least nine distinctive proteins, five of which can be conveniently characterized as sedimentation boundaries in the analytical ultracentrifuge; some of the members of this large group seem to be structurally interrelated, and hence may prove to be antigenically related. Several of them are iodo proteins and glycoproteins. With respect to the tissue specificity, the highly specific activity that is seen is based on the 19S thyroglobulin. This large and complex molecule, when examined from a variety of animal species, shows a complex and inexplicable pattern of antigenic similarities, and differences suggesting that larger or smaller portions of the molecule are essentially the same in certain groups of species and not in others.