AIM To quantify the intraepithelial lymphocytes (IELs) and to document the membrane expression of CD4, CD8, TCRgamma delta and adhesion and/or activation-associated molecules (CD103, CD28, CD44, CD69, HLA-DR, CD95/Fas) in the duodenal mucosa of patients with functional dyspepsia (FD) in order to provide arguments for an immunological process in FD. METHODS Twenty-six FD patients according to Rome II criteria (20 were H pylori negative) were studied and compared to 12 healthy adults. IELs were isolated from five duodenal biopsy samples, then quantified by microscopy and flow cytometry while the membrane phenotypes were determined by cytofluorometry. RESULTS Duodenal histological examination was normal. In H pylori negative patients, the number of IELs was not different from that in healthy controls. Median percentage expression of CD4, CD8, or TCRgamma delta and CD103, CD44, CD28, CD69 on CD3+ IELs, among the adhesion/activation associated molecules tested, was not different from that in healthy controls. In contrast, the median percentage expression of CD95/Fas [22 (9-65) vs 45 (19-88), P=0.03] and HLA-DR expressing CD3+ IELs [4 (0-30) vs 13 (4-42), P=0.04] was significantly lower in the H pylori negative FD group than in healthy controls, respectively. The number of IELs was significantly greater in H pylori positive FD patients than in healthy controls [median ratio for 100 enterocytes 27.5 (6.7-62.5) vs 10.8 (3-33.3), P=0.02] due to a higher number of CD8+ CD3+ IELs. CONCLUSION In H pylori negative FD patients, the phenotypic characterization of IELs suggests that we cannot exclude a role of IELs in FD.