Nitric oxide (NO) can exert both protective and proinflammatory actions in the gastrointestinal tract. NO, formed physiologically by constitutive NO synthases, regulates vascular tone, protects the microvasculature from injury, and modulates adhesion of inflammatory cells. In contrast, expression of an inducible isoform of NO synthase, capable of producing excessive NO levels, is implicated in tissue injury. Such proinflammatory effects of NO, observed in epithelial and endothelial cells, may depend on degree of expression, as well as local environment, and involve further cytotoxic moities such as peroxynitrite. Therapeutic potential of selective inhibitors of NO formation is thus anticipated.