Persistent diarrhea, vomiting, and dehydration are symptoms often seen in patients suffering from food allergy after chronic antigen exposure; however, the precise mechanisms involved have not been well defined. In an effort to clarify the mechanisms of the chronic intestinal changes attributable to genuine IgE-mediated anaphylactic reactions induced by orally administered antigen, a mouse model was established by s.c. implantation of a murine hybridoma capable of producing monoclonal antitrinitrophenyl IgE antibody, and the morphologic and immunologic changes occurring in the intestine upon chronic antigen exposure were investigated. In the early stage after ingestion of the antigen, diarrhea and noticeable infiltration of mast cells as well as eosinophils into the lamina propria were observed. A substantial increase in serum histamine levels as well as an increase in leukotriene C4 synthesis in the jejunal mucosa were observed 1 h after antigen challenge. Also, the synthesis of leukotriene B4 was significantly elevated for up to 9 h after antigen challenge. The expression of both intercellular adhesion molecule-1 (ICAM-1) on mucosal vascular endothelial cells and IAd on epithelial cells was markedly enhanced, and noticeable infiltration of eosinophils and lymphocytes was also confirmed in the mouse model after chronic antigen exposure. These findings suggest that oral antigen exposure induces anaphylactic reactions in the intestine mediated by mast cells and eosinophils in response to the IgE-antigen complex in the early phase, and also induces lymphocyte migration after chronic antigen exposure.