Understanding of the formation and biological actions of nitric oxide (NO) has grown extensively during the past 2 decades. Through our discoveries of the biological effects of NO and nitrovasodilators on cyclic guanosine monophosphate (GMP) and our discoveries of the biochemical mechanisms of NO and regulation of NO synthase in numerous cell types and tissues, the complexity of the signal transduction cascade and the extensive function-regulating interactions of the NO molecule have been increasingly demonstrated. Although the diverse roles of this unique molecule continue to unfold, NO can be recognized as an intracellular second messenger, a local substance for regulation of neighboring cells, a neurotransmitter in central and peripheral neurons, and perhaps a hormone that can act at distant sites and has been shown to have beneficial or deleterious biological effects, depending on its concentration, the system, and the cellular environment.