We investigated whether sensitization to cow's milk occurs during malnutrition and alters intestinal ion and macromolecular transport. Malnourished guinea pigs received a low-protein diet containing either 4% soy or 4% milk proteins, and well-nourished sensitized controls received 26% soy plus 4% milk proteins. To assess milk sensitization, we measured immunoglobulin (Ig) G and passive cutaneous anaphylactic (PCA) responses to beta-lactoglobulin (beta-Lg) and the intestinal anaphylaxis, reflected by the rise in short-circuit current (delta Isc) induced by beta-Lg in tissues mounted in Ussing chambers. To assess intestinal function, we measured ionic conductance and unidirectional fluxes of -14C-mannitol and -3H-horseradish peroxidase (HRP). In malnourished animals fed milk proteins, IgG, PCA, and delta Isc (beta-Lg) increased more than in well-nourished animals. Ionic conductance and mannitol permeability rose in both malnourished groups. Malnourished animals fed milk proteins also displayed enhanced permeability to HRP. These data suggest that increased paracellular permeability is due to malnutrition per se, whereas increased macromolecular transport seems to require both malnutrition and sensitization. They indicate that intestinal anaphylaxis in response to milk proteins is persistent and even enhanced during experimental malnutrition.