This antibody reacts with serotonin-containing cells in a wide range of normal, reactive, and neoplastic tissues. Other endocrine cells, such as those of pancreatic islets and pituitary gland, are negative with this antibody. Preabsorption of the antibody with serotonin abolishes any positive reaction. Serotonin-positive cells are present in gastric, duodenal, jejunal, ileal, colonic, and appendiceal mucosae. Positive cells are sparse and usually occur in the lower half of the gastric and intestinal mucosae. In the appendix, in addition to the mucosal serotonin-containing cells, there are single or small clusters of serotonin-positive cells in the sub-epithelial region of the lamina propria. A wide range of reactive, hyperplastic and metaplastic epithelia may contain serotonin-positive cells. These include hyperplastic polyps of gastro-intestinal tract, chronic cholecystitis with intestinal metaplasia, and chronic cystitis glandularis. Carcinoids are the primary serotonin producing neoplasms. Those of appendix or small intestine give a positive immunohistological reaction for serotonin, but those occuring in the rectum, stomach, or lung, may or may not contain this substance. Other normal tissues which may contain serotonin-positive cells include the central nervous system, adrenal medulla, normal paraganglia of carotid, retroperitoneum, and normal bronchial epithelium. A variety of non-endocrine adenocarcinomas may also contain a few serotonin-positive cells. These include adenocarcinomas of upper respiratory tract, lung, gastrointestinal tract, gall bladder, pancreas, urinary bladder, prostate, female genital tract, and breast. Serotonin is also demonstrable in many paragangliomas.