A rationale for sequential immunohistochemical studies of the endocrine function of APUD cells is described, as exemplified by a study of serotonin-containing cells in rat small intestine, involving preparation of paraffin and semithin sections of epoxide resin-embedded tissue, followed by electron-microscopic examination of cells detected by the immunoperoxidase technique. With the approach described, it has been shown that a positive immunohistochemical reaction to antiserotonin antiserum is given, along with EC cells, by those mast cells disposed in groups near the EC cells as well as among connective-tissue cells of villi under the basement membrane. It is suggested that by collecting and accumulating the serotonin synthesized by specialized EC cells, mast cells transport it to sites of utilization as required by the specific arrangement.