The presence of thyroid-stimulating immunoglobulins in patients with Graves' disease is well established. Considerable evidence has accumulated that these immunoglobulins are antibodies to a thyroid plasma membrane antigen whose precise nature remains to be identified. The question whether the antigen is related to the TSH receptor is still debated. The causative role of thyroid-stimulating immunoglobulins in the hyperthyroidism of Graves' disease is widely recognized. The use of human specific stimulation assays has circumvented the objection of the relatively low frequency of long-acting-thyroid-stimulator-(LATS)-positive patients. Individual variations in the thyroid response may account for the lack of correlation between the levels of thyroid-stimulating immunoglobulins and most parameters of thyroid function. In this respect, the interference of nonstimulatory thyroid antibodies and of other autoimmune mechanisms may be of importance. An important clinical implication of thyroid-stimulating immunoglobulin determinations is their value in predicting the relapse of hyperthyroidism in treated patients. This clinical application has been so far limited by the technical difficulties of the assays. This emphasizes the need for a simple and reliable test, which can be used for routine measurements of thyroid-stimulating immunoglobulins.