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AIMS: To substantiate that incubation with monoclonal antibody CD15 (C3D-1) elicits a distinctive immunoreaction in normal small intestinal Paneth cells, normal and metaplastic Paneth cells along the digestive tract were assessed to determine whether they are also immunoreactive to CD15. METHODS: Paneth cells in paraffin wax embedded specimens of normal small intestine, appendix and proximal ascending colon, and from cases of chronic gastritis and ulcerative colitis were investigated immunohistochemically for lysozyme and CD15 antigen expression by means of the avidin-biotin peroxidase complex method. RESULTS: CD15 antibody reacted with a high proportion of both normal and metaplastic Paneth cells. Paneth cell immunoreactivity to CD15, however, was less intense and less extensive than to antilysozyme antibody, though the latter also stained many other cell types and was more commonly associated with nonspecific background staining. CONCLUSIONS: CD15 seems to be a valuable adjuvant for the study of Paneth cells in the normal and diseased digestive tract. Furthermore, as CD15 has been shown to be involved in activation of phagocytes, its expression in Paneth cells reinforces their proposed role as antimicrobial agents and regulators of the intestinal flora.