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There is now considerable clinical evidence that oats do not activate coeliac disease. Nonetheless, a reluctance to include oats in the gluten-free diet remains. Because gluten-induced damage is accompanied by activation of the gastrointestinal immune system, the purpose of this study was to investigate if similar changes were induced by oats ingestion. Small intestinal histological sections from 10 patients who ingested 50 g of oats daily for 3 months were investigated for possible evidence of immune activation. Tissue obtained before and after oats challenge was stained with a series of antibodies directed against the following molecules: human leucocyte antigen D-related (HLA-DR), Ki-67, CD25, CD54 [intercellular adhesion molecule 1 (ICAM-1)] and mast cell tryptase. None of the patients developed clinical or laboratory evidence of adverse effects. The distribution of intestinal HLA-DR expression was not affected by oats ingestion and the crypt epithelium remained unstained. In the pre-oats biopsies, the percentage of Ki-67 positive enterocytes, 29·5 ± 6·9 [95% confidence interval (CI) 13·9–45·0] did not differ significantly from that found in postoats biopsies, 41·2 ± 3·7 (95% CI, 32·8–49·6), P = 0·19, not significant. Furthermore, oats ingestion did not alter the number of CD25 positive and tryptase positive cells. Finally, the distribution and intensity of ICAM-1 staining was unchanged by dietary oats. In summary, detailed immunohistological studies of biopsies from patients ingesting oats for 3 months did not reveal evidence of immune activation. Together with other reported findings, this study strengthens the view that oats can be included safely in the diet of gluten sensitive patients.