In this article, the evidence for the involvement of free radicals in some of the gastrointestinal disorders is reviewed. Oxygen radicals are partially reduced oxygen species that include superoxide, and hydroxyl radicals, and hypophthalous acids. Most cells possess numerous antioxidant enzymes and scavengers to protect themselves from these injurious agents; the rate of production of reactive oxygen metabolites may exceed the capacity of the antioxidant defenses thus resulting in tissue damage. The gastrointestinal tract is particularly well endowed with the enzymatic machinery necessary to form large amounts of oxygen radicals. Sources of radicals in the gastrointestinal tract include mucosal xanthine oxidase and NADPH oxidase found in the resident phagocytotic leukocytes (macrophages, neutrophils, eosinophils) of the lamina propria. Other sources of oxygen radicals in the gastrointestinal tract involve ischemia and reperfusion, drug ingestion, diet and radiation therapy. Recent studies have demonstrated the involvement of oxygen radicals following active episodes of small-intestinal ischemia, ulcerative colitis, pancreatitis and gastric ulcer. In contrast to cell antioxidants, control of tissue free radical levels is now pharmacologically feasible and perhaps justified for specific diseases. However, carefully designed and controlled clinical trials are needed.