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 beta-lactoglobulin and by intestinal anaphylaxis measured in Ussing chambers by the increase in short circuit-current after addition of beta-lactoglobulin (Delta ISCbeta Lg). Oxidative stress was assessed by intestinal lipid peroxidation. The intestinal secretion was assessed by Delta ISC induced by inflammatory mediators. Malnutrition increased the level of anti-beta Lg 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 (Delta ISCbeta Lg = 16.4 +/- 9.9 and 9.1 +/- 5.8 mu A/cm(2) 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 (Delta ISCbeta Lg = 2.8 +/- 2.5 mu A/cm(2) 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.