The adenyl cyclase, cAMP-binding and protein-kinase activities have been studied in thyroid glands from patients with Graves' disease in comparison with normal thyroid glands. The basal and TSH-stimulated adenyl cyclase activities were tested in crude plasma membrane preparations. The characteristics of the intracellular binding of cAMP, i.e., the maximal binding capacity (MBC) for cAMP and affinity constant (Ka) of the binding, and the basal and cAMP-stimulated protein-kinase activities, were estimated in both the soluble and particulate fractions of thyroid tissue. All of these parameters studied were essentially normal in Graves' disease. It is concluded that hyperthyroidism in Graves' disease is probably not a result of qualitative or quantitative abnormalities in the adenyl cyclase-cAMP protein-kinase system.