BACKGROUND To improve the diagnosis of intestinal allergy, we developed a colonoscopic allergen provocation (COLAP) test. METHODS The cecal mucosa was challenged with three food antigen extracts, a buffer control and a positive control (histamine). The mucosal wheal and flare reaction was registered semiquantitatively 20 min after challenge, and selected tissue biopsies were examined for mast cell and eosinophil activation by immunohistochemistry and electron microscopy. The COLAP test was performed on 70 adult patients with abdominal symptoms suspected to be related to food allergy and in 5 healthy volunteers. In parallel, skin prick tests were performed and IgE was measured in serum. RESULTS 97 out of 210 antigen challenges performed in the patient group induced a significant wheal and flare reaction of the mucosa (46%), whereas no reaction in response to antigen was observed in healthy volunteers. Antigen-induced wheal and flare reactions were dependent on patients' histories of adverse reactions to food, but not on serum levels of specific IgE or skin test results. Degranulation of mast cells was observed in almost all tissues in which food antigens caused a wheal and flare reaction. Eosinophil activation was also highly correlated with the extent of the wheal and flare reaction (r(s) = 0.86). CONCLUSIONS The data suggest that the COLAP test may be a useful diagnostic means in patients with suspected intestinal food allergy and a new tool for the study of underlying mechanisms.