Background:Although a high level of intraepithelial lymphocytes (IELs) has been demonstrated in intestinal biopsies from children with cow's milk protein intolerance (CMPI), the properties of IELs in food‐sensitive enteropathies remain unclear. In the present study, we analyzed the cytotoxic potential of IELs in CMPI, using a monoclonal antibody directed against the cytotoxic granule‐associated protein TIA1.Methods:The study included 18 duodenal biopsies from 10 children previously diagnosed with CMPI and on a cow's milk‐free diet of various duration. Six normal duodenal biopsies from children free of food intolerance served as controls. Immunostaining of formalin‐fixed tissues was used to determine in the intraepithelial compartment (1) the number of TIA1‐expressing cells per 100 epithelial cells, (2) the number of IELs per 100 epithelial cells, (3) the ratio of TIA1‐expressing IELs (TIA1/IEL ratio).Results:In CMPI, the number of IELs and TIA1‐positive cells, as well as the TIA1/IEL ratio was significantly increased compared with controls. Moreover, a negative correlation between the TIA1/IEL ratio and the duration of the diet was observed.Conclusions:These results suggest that the recruitment of IELs with cytotoxic potential is increased in CMPI, and that IEL‐mediated cytotoxicity could be involved in the pathogenesis of the disease.