Organic nitrates, molsidomine and sodium nitroprusside belong to a group of vasodilators containing an NO-group. Although some of them have already been used in the therapy of cardiovascular diseases for decades and although numerous results have been accumulated on their effects on the cardiovascular system as well as on isolated organs, the mechanism of their action on a cellular level is still to be explained. The metabolite of molsidomine used in ischemic heart disease, 3-morpholino-syndnonimine (SIN-I) and other sydnonimines have a vasodilatory effect and, like sodium nitroprusside, inhibit platelet aggregation, which possibly contributes to the therapeutic effect. It was shown that SIN-I raises the content of cyclic GMP of various blood vessels and, like other sydnonimines. raises the cyclic GMP concentration of platelets to an extent similar to that seen with sodium nitroprusside. SIN-I and other sydnonimines stimulate the soluble cyclic GMP-forming enzyme from hog spleen arteries and from human platelets: the same holds true for the soluble guanylate cyclase purified from bovine lung. On the basis of results from reaction-kinetic experiments performed with sydnonimines and soluble guanylate cyclase, it can be assumed that the enzyme is directly activated by the A-forms of sydnonimines which are non-enzymatically formed and contain an N-NO-group. On the basis of these and other findings, it is likely that the active metabolites of NO-containing vasodilators are compounds whose NO-group can be bound through nitrogen, oxygen or sulfur. The findings obtained so far on the regulation of cyclic GMP formation by hormonal factors and drugs as well as on the effects of cyclic GMP derivatives on smooth muscle and platelets suggest that cyclic GMP-dependent regulatory processes are involved in the effects of NO-containing vasodilators. It can be expected that the elucidation of cyclic GMP-dependent regulatory processes will contribute significantly to the understanding of the differences in effects of these drugs on capacity and resistance vessels, of the tolerance development when organic nitrates are used and of possible interferences with other cardiovascular-active drugs such as β-blockers or calcium antagonists.