The recent discovery of nitric oxide ('NO)'as a mammalian metabolic intermediate has exploded into a swiftly developing area of research. The intense interest and rapid progress have developed primarily because (i)'NO synthesis has been found in a variety of different cell types,(ii)'NO controls and influences a number of critical physiological processes, and (iii)'NO synthesis via the oxidation of L-arginine has been shown to involve unusual oxidative chemistry and has uncovered novel aspects of eukaryotic enzymology. The formation of'NO from L-arginine in mammalian cells is catalyzed by the enzyme'NO synthase (NOS, EC 1.14. 13.39)(Scheme I). The best characterized examples of biological reactions controlled by'NO include vasodilation and regulation of normal vascular tone, inhibition of platelet aggregation, neuronal transmission, and cytostasis (for reviews, see Refs. 1-4). In addition to these activities it appears that abnormally high levels of'NO are also involved in the hypotension associated with endotoxic shock (5), inflammatory response-induced tissue injury (61, mutagenesis (7, 8), and the formation of carcinogenic N-nitrosamines (9). In tissues where'NO controls normal vascular tone, low levels can also be deleterious such as in the case of pulmonary hypertension in infants and adults.'NO has very recently been found to be useful in the treatment of this type of hypertension.