Nitric oxide (NO) plays important roles in physiology and pathology. This small molecule regu-lates smooth muscle tone, functions as a neuro-transmitter, regulates cellular proliferation, and protects the host against neoplasia and infection (1). NO may also mediate deleterious effects. For example, it appears to be important in inflamma-tion, carcinogenesis, aging, and neurotoxicity (1-3). NO is produced from L-arginine by the actions of NO synthases (NOS), a family of enzymes encoded by separate genes (4, 5). Neuronal NOS (NOSI, found mainly in neuronal cells and skeletal muscle cells) and endothelial NOS (NOS3, found mainly in endothelial cells) are produced constitutively. Their actions are controlled in large part by changes in intracellular calcium concentrations, and NOS1 and NOS3 generate low-level NO production. Inducible NOS (iNOS or NOS2) is expressed by numerous cell types, but mainly by mononuclear phagocytes, hepato-cytes, chondrocytes, and smooth muscle cells (5, 6). Activity of NOS2 is controlled primarily by regulation of mRNA transcriptionand translation. Under proper conditions, NOS2 produces very high levels of NO. The overall production of NOS2 and NO is influenced by many factors (Fig. 1). Regulation of NOS2 mRNA can occur at multiple steps (see ref. 5 for review), including mRNA transcription, mRNA stability, mRNA translation, and mRNA level (precise mechanisms not known). At the protein level, NOS may be regulated in many ways: by calmodulin binding, dimer formation