In retrospect, basic research in the fields of NO and cyclic GMP during thev past two decades appears to have followed a logical course beginning with the findings that NO and cyclic GMP are vascular smooth muscle relaxants, that nitroglycerin relaxes smooth muscle by metabolism to NO, progressing to the discovery that mammalian cells synthesize NO, and finally the revelation that NO is a neurotransmitter mediating vasodilation in specialized vascular beds. A great deal of basic and clinical research on the physiological and pathophysiological roles of NO in cardiovascular function has been conducted since the discovery that EDRF is NO. The new knowledge on NO should enable investigators in this field to develop novel and more effective therapeutic strategies for the prevention, diagnosis and treatment of numerous cardiovascular disorders. Since NO elicits a protective and beneficial action in many disease states, novel NO donor drugs for clinical use should prove to be very effective drugs for the treatment of essential hypertension, stroke, coronary artery disease, vascular complications of diabetes, impotency and other disorders involving the vascular system.