Raised levels of circulating natural antibodies (NABS) have been found in association with systemic lupus erythematosus (SLE) and chronic active hepatitis (CAH), indicative of polyclonal B-cell activation associated with these relatively non-organ specific autoimmune diseases. This study examined the natural antibody response in the organ-specific autoimmune disease Hashimoto's thyroiditis. Serum samples obtained from 69 women with newly diagnosed Hashimoto's thyroiditis together with 64 controls were analysed for IgG and IgM NABS directed at DNA, actin, myoglobin, myosin, trinitrophenyl hapten (TNP) and tubulin as the NAB antigen panel using an established ELISA. The same technique was also used to estimate thyroglobulin and thyroid microsomal autoantibody activities. Compared to a reference panel of normal serum samples, 31 of the Hashimoto's samples showed a greater than 2SD elevation of IgG and/or IgM NABS against one or more of the panel antigens together with elevated IgG thyroglobulin and thyroid microsomal antibody levels. The cases positive for one or more of the NAB panel also showed a greater incidence of active Hashimoto's thyroiditis as indicated by the presence of antibodies directed against the thyroid specific antigens. The above findings suggest that raised levels of NABS are also a feature of this organ-specific autoimmune disease. The wide ranging NAB specificities involved are consistent with an underlying or epiphenomenal state of polyclonal B-cell activation.