Cyclic AMP probably plays an important role in blood-vessel relaxation caused by beta-adrenergic agonists and other agents, including inhibitors of cyclic nucleotide phosphodiesterases. Cyclic GMP may participate in blood-vessel relaxation caused by drugs such as nitroglycerin and nitroprusside and by agents that require the endothelium for their relaxing effects. The significance of elevated levels of cyclic GMP in response to contraction-producing agents is unknown. Cyclic nucleotides may modulate vascular smooth-muscle contraction by regulating the phosphorylation of multiple proteins involved in the action and distribution of calcium. The relative importance of different potential sites of regulation by cyclic nucleotides may vary among different blood vessels.