Owing to poor reliability of laboratory tests, diagnosis of food allergy is based on clinical response to double-blind placebo-controlled food challenge. The aim of the present study was to assess the value of duodenal IgE-positive cells in the diagnosis of food allergy. Thirty-one children with a history of possible food allergy underwent duodenal biopsies, skin prick tests, and measurement of serum IgE antibodies, and were put on an elimination diet followed by food challenge. Open food challenges were performed in patients under 12 mo of age, and double-blind placebo-controlled challenges were for suspected foods. On the basis of clinical food hypersensitivity, patients were divided into two groups. Group 1 consisted of 13 children with food allergy. Thirteen of 20 positive provocations elicited reactions within 12 h from the end of the challenge, seven later. Group 2 was the control group and included 18 patients with negative food challenges. The number of IgE-positive cells in biopsy specimens was significantly more elevated in group 1 with respect to group 2 (153.24 +/- 83.13 versus 18.4 +/- 18.9; p < 0.01). Total serum IgE levels were elevated compared with that of the control group (p < 0.01) and correlated with the number of IgE-positive cells (p < 0.001, r = 0.62). Enhanced IgE-containing cells were found in all delayed reactors, but about one-third had negative skin prick tests or specific serum IgE antibodies to the offending foods. Our results showed that systemic reactions to foods are associated with an IgE-mediated response in the duodenal mucosa. Larger studies would be required to assess the predictive value of an increased number of IgE-positive cells in the diagnosis of allergy to food, especially in children with delayed reactions.