Weaning is a transient period of life during which maternal proteins are replaced by foreign proteins. Concomitantly, in early postnatal life, both digestive and immune systems undergo a maturation process. Allergy to cow's milk protein may develop in human infants during weaning, determining digestive, respiratory, cutaneous or systemic symptoms. We studied the intestinal response to bovine milk beta-lactoglobulin (beta-LG) in infants with cow's milk allergy, first during the active phase, and then during the symptom-free stage. During the active phase, transepithelial transport of the beta-LG across the intestinal epithelial layer stimulated the sensitized subepithelial immune cells. This stimulation induced a rise in short-circuit current suggestive of an electrogenic chloride secretion and impaired protein handling by the epithelium. These findings underline the dual role of the epithelial layer in intestinal function: on one hand, it takes an active part in allowing dietary antigens to stimulate the submucosal system, and on the other hand becomes the target for mediators involved in food allergy.