The effects of anti-receptor (anti-idiotypic) immunity on autoimmune responses have been investigated in Buffalo (BUF) rats with autoimmune thyroiditis. As compared to other animal models of autoimmune disease, BUF rat thyroiditis has the following advantages: it occurs in an inbred strain, arises spontaneously (i.e. without the experimental administration of autoantigens and adjuvants) and is characterized by production of autoantibodies to only one autoantigen, thyroglobulin. Finally, its pathogenesis is mediated by autoantibodies to rat thyroglobulin, and therefore this model is particularly suitable to study the effects of anti-idiotypic reactions on those autoimmune disorders whose damage is caused by humoral immunity. The experiments reported in the present study show that first, heterologous anti-idiotypic antibodies to autoantibodies against rat thyroglobulin have been produced and characterized. It has then been demonstrated that such anti-idiotypic antibodies are capable of inhibiting the in vitro binding between thyroglobulin and thyroglobulin autoantibodies obtained from BUF rats. It has also been shown that repeated injections of anti-idiotypic antibodies into sublethally X-irradiated BUF rats with autoimmune thyroiditis were followed by a significant change in the levels of circulating autoantibodies to rat thyroglobulin. These results provide evidence that in spite of the complexity of autoantigens and the heterogeneity of autoimmune responses, established autoimmune diseases may be controlled by sequential immunosuppression and anti-idiotypic immunity.