Summary: Circulating thyroid autoantibodies have been produced in mice by the injection of either homologous or heterologous (rat and rabbit) thyroid extract incorporated in complete Freund adjuvant. Rat thyroid extract injected without adjuvant also was capable of eliciting antibodies directed against both rat and mouse thyroid extract. Even though normal animals did not respond to aqueous mouse thyroid extract (MTE), animals previously sensitized with the same antigen in complete Freund adjuvant, or syngeneic recipients of lymphoid cells from sensitized donors, readily responded to a similar injection. These results imply the production of a new population of responsive cells following initial stimulation. Histologic examination of thyroid glands from inbred mice sensitized under a wide variety of conditions revealed no pathologic changes despite the presence over a long period of time of circulating antibody demonstrated by tanned cell hemagglutination and passive cutaneous anaphylaxis.