The synthesis of cyclic GMP from GTP is catalysed by three isoenzyme forms of guanylate cyclase which include the soluble or cytosolic form, the particulate or membraneassociated form and a form associated with the cytoskeletal components (see reviews [ l , 21). These isoenzymes have different physiochemical, antigenic and kinetic properties and will undoubtedly have different primary structures. Each of these isoenzymes has different mechanisms for their regulation, which in our detailed studies described elsewhere, have proved to be rather complex (see reviews [ 1,2]). When we were characterizing and purifying these isoenzymes some years ago, we found that azide, hydroxylamine and nitrite activated the enzyme [3]. Since these were the first agents to activate the enzyme in cell-free preparations, we conducted a series of detailed studies to determine the mechanisms involved (see reviews [ 1, 21). Fortunately at the time we were also examining cyclic GMP metabolism in tracheal smooth muscle preparations [4, 51. We found that these and other agents such as nitroglycerin and nitroprusside activated guanylate cyclase, increased cyclic GMP synthesis and resulted in smooth muscle relaxation [4, 51. We