Zinc supplementation could favor recovery from diarrhea in malnourished children. As the recent experimental evidence suggests that oxidative stress and intestinal anaphylaxis may contribute to the intestinal dysfunction associated with malnutrition, we postulated that zinc could act through antioxidant or antianaphylactic properties. Control (C), malnourished (M), and malnourished zinc-treated (MZ) guinea pigs were, respectively, fed a normal 30% protein diet, a low 4% protein diet, and a low 4% protein diet plus 1800 ppm of zinc. Milk proteins were included in the diets to trigger intestinal anaphylaxis. Milk sensitization was assessed by passive cutaneous anaphylaxis(PCA) against β-lactoglobulin and by intestinal anaphylaxis measured in Ussing chambers by the increase in short circuitcurrent after addition ofβ-lactoglobulin (ΔIscβLg). Oxidative stress was assessed by intestinal lipid peroxidation. The intestinal secretion was assessed by ΔIsc induced by inflammatory mediators. Malnutrition increased the level of anti-βLg reaginic antibodies [PCA = 1.19 ± 0.79 and 0.69 ± 0.67 log(1/titer) in M versus C guinea pigs, p = 0.07] and enhanced intestinal anaphylaxis(ΔIscβLg = 16.4 ± 9.9 and 9.1 ± 5.8μA/cm2 in M versus C guinea pigs, p = 0.07), without inducing intestinal lipid peroxidation. Moreover, malnutrition enhanced significantly the intestinal secretory response to histamine and 5-hydroxytryptamine. Administration of pharmacologic doses of zinc during malnutrition inhibited the increase in milk sensitization induced by malnutrition, both at the systemic [PCA = 0.35 ± 0.55 log(1/titer) in MZ guinea pigs, p = 0.03 versus M] and intestinal(ΔIscβLg = 2.8 ± 2.5 μA/cm2 in MZ guinea pigs; p = 0.001 versus M) level, and prevented the hypersecretion in response to histamine and 5-hydroxytryptamine. These data suggest that zinc has antianaphylactic and antisecretory properties that may contribute to its capacity to prevent intestinal dysfunction during malnutrition.