During immunohistochemical studies of cyclooxygenase-2 (COX-2) on human colon cancers, many strong COX-2-immunoreactive cells scattered in the bottom of the crypt of normal colon mucosa were unexpectedly noticed. COX-2-immunoreactive cells were morphologically very similar to neuroendocrine cells and were confirmed immunohistochemically to be positive for chromogranin A or serotonin. Moreover, COX-2-immunoreactive neuroendocrine cells were observed not only in the large intestine, but also in the stomach, duodenum and small intestine. The role of COX-2 expression in neuroendocrine cells of the human alimentary tract was speculated.