Recent clinical and experimental findings have reinforced the link among zinc deficiency, malnutrition and diarrheal disease. Because there is a strong association between protein and zinc content in virtually all types of foods, insufficient protein intake may often be the cause of zinc deficiency. Compensatory mechanisms operating in monogastric species during malnutrition are less effective for the absorption of transition divalent elements such as zinc, which remain bound to ligands of dietary or endogenous origin. Both protein and zinc deficiencies are strong negative determinants for normal cellular immunity. In zinc deficiency, the organism is more susceptible to toxin-producing bacteria or enteroviral pathogens that activate guanylate and adenylate cyclases, stimulating chloride secretion, producing diarrhea and diminishing absorption of nutrients, thus exacerbating an already compromised mineral status. In addition, zinc deficiency may impair the absorption of water and electrolytes, delaying the termination of normally self-limiting gastrointestinal disease episodes. The gastrointestinal tract may be one of the first target areas where zinc insufficiency may be manifested. A prolonged low zinc intake deprives the organism of the local potential beneficial effects of zinc, including interactions with oxidative free radicals and nitric oxide metabolism. Nitric oxide is a second messenger that plays an important part in the triggering of diarrheal disease. The possible interrelationship among infection, inflammation, free radical damage and its quenching by potential scavengers, such as zinc, in the intestinal lumen or within the enterocyte should be more extensively studied.