12-Lipoxygenase enzyme oxygenates the position 12 of arachidonic acid, and produces 12S-hydroperoxy-arachidonic acid. When mouse gastrointestinal tract was immunostained with an antiserum against human platelet 12-lipoxygenase and examined by light microscopy, positively-stained cells were found in the epithelium of stomach and small and large intestines. Electron microscopic immunohistochemistry revealed that the positively-stained cells were open-type enteroendocrine cells. The endocrine cells had many granules of heterogeneous sizes, forms and internal structures, and most of the granules had electron lucent area. 12-Lipoxygenase was localized in the cytoplasm, but not in the nucleus, plasma membranes and other subcellular organelles. Double immunostaining revealed that all 12-lipoxygenasepositive cells contained serotonin. With an antiserum against 12-lipoxygenase isozyme of porcine leukocytes, no positively-stained cells were observed in gastrointestinal epithelium.