Nitric oxide (NO) production, as detectable by indirect and direct methods, as well as the expression of inducible nitric oxide synthase (iNOS) in the intestinal mucosa appear to be enhanced in active ulcerative colitis and, when in excess, to play a proinflammatory role in the disease. Despite some conflicting data, there is evidence that NO production is also increased in Crohn's disease. Many inflammatory features of inflammatory bowel disease are in keeping with the physiological properties of NO, and toxic megacolon, a complication of chronic colitis characterized by acute colonic dilatation, is associated with an enhanced intestinal synthesis of NO. The drugs currently used in the treatment of inflammatory bowel disease (steroids, salicylates) do not seem to exert substantial effects on intestinal NO synthesis. The possible therapeutic role of selective iNOS inhibitors is still under investigation.