Using a radioreceptor assay and serum immunoglobulin(Ig) prepared by ammonium sulfate precipitation, significantTSH displacement activity (TDA) was demonstrated in5 of 15 patients with subacute thyroiditis tested during the acutephase. Using a cAMP generation assay, adenyl cyclase stimulationby Ig from patients with subacute thyroiditis was notdemonstrated. The nature of the TDA demonstrated in subacutethyroiditis was investigated to determine whether the factormeasured was TSH receptor antibody, as is found in Graves’hyperthyroidism, or thyroglobulin, which is know to give falsepositive responses in the radioreceptor assay. When Ig wasprepared by DEAE+-Sephadex chromatography, mean TSHdisplacement indices were similar to those given by ammoniumsulfate-prepared Ig for both Graves’ disease and subacute thyroiditis.On the other hand, when Ig was prepared by DEAE+-cellulose chromatography, which isolates highly purified IgG, mean indices were significantly less than for ammonium sulfatepreparedIg for both Graves’ hyperthyroidism and subacutethyroiditis. Thyroglobulin was not detected in Ig prepared byany of the 3 methods. Although high concentrations of crudethyroid-soluble fraction and purified thyroglobulin gave stronglypositive responses in the radioreceptor assay, concentrations ofthyroglobulin over the range found in the sera of patients withsubacute thyroiditis could not be shown to give positive responses.Moreover, TSH displacement indices did not correlatewith serum thyroglobulin levels. As determined by species crossreactivityand dose-responses studies, the TDAs demonstratedin subacute thyroiditis and Graves’ hyperthyroidism were similar.It was concluded that the TDA demonstrated in subacutethyroiditis represents antibody which binds to, but does notstimulate, the TSH receptor.