Irrespective of where ulceration occurs in the gastrointestinal tract, it is almost always associated with mucosal inflammation. The chemical mediators that coordinate inflammatory responses also have the capability to alter the resistance of the mucosa to injury. Some inflammatory mediators increase the resistance of the mucosa to injury, while others exert "ulcerogenic" effects. In this review, we provide an overview of the major inflammatory mediators that have been shown to exert effects on mucosal defense in the gastrointestinal tract. Among the inflammatory mediators discussed are the eicosanoids (prostaglandins, leukotrienes, thromboxanes), nitric oxide, neuropeptides, and cytokines (IL-1beta, TNF alpha). Several of these mediators are considered potential therapeutic targets for the treatment of ulcerative diseases of the digestive system, and, in some cases, clinical data are available on the efficacy of such approaches.