The recent discovery that mammalian cells can synthesize nitric oxide coincided with the identification of this simple gas as a factor involved in cellular communication. Nitric oxide has now been shown to be derived from L-arginine in macrophages, endothelial cells and possibly other cell types. Its physiological role in macrophages may be as a cytotoxic agent. However, nitric oxide produced by endothelial cells is thought to trigger vascular smooth muscle relaxation through activation of the enzyme guanylate cyclase.