Mast cells are a significant component of the mucosa in the gastrointestinal tract. There is increasing evidence that these cells are involved in the pathophysiology of various intestinal disorders ranging from food allergy to inflammatory bowel disease. When activated, mast cells release a host of potent mediators and cytokines which are capable of inducing pathophysiology. The bulk of the evidence has come from hypersensitivity studies in experimental animals sensitized either by parasitic infection or by active immunization to an antigen using adjuvants which stimulate IgE production. Subsequent antigen challenge of the gut results in mast cell activation associated with alterations in intestinal functions including ion transport and epithelial permeability. Intestinal secretory transport responses are inhibited by antagonists of mast cell mediators and neurotoxins, implicating mast cell-nerve interactions with the epithelium. In genetically mast cell-deficient mice, antigen-induced secretion is reduced approximately 70% and this component is not affected by neural or mast cell inhibitors; adoptive transfer of bone marrow containing mast cell precursors derived from congenic normal mice restores the complete antigen response. These results provide more direct proof that mast cell activation causes abnormal gut function. Recently, we have begun studies which indicate that activation of mast cells induces ion secretion in surgically resected human intestine. Reduced secretory responses in specimens from patients with IBD suggest that mast cells may play a role in the pathophysiology of inflammatory bowel disease.