Chromogranin A, the major soluble protein costored and coreleased by exocytosis with catecholamines from the adrenal medulla, has recently been detected in several bovine polypeptide hormone producing tissues. We therefore searched for chromogranin, by immunohistology, in human polypeptide hormone producing tumors as well as normal human endocrine tissues. The chromogranin A antigen was purified from catecholamine storage vesicles of human pheochromocytoma, to which rabbit antisera were developed, allowing immunohistologic studies by the indirect rabbit anti-peroxidase technique. Specific chromogranin staining was noted in all polypeptide hormone producing human tumors studied (pheochromocytoma chromaffin cells, n = 3; medullary thyroid carcinoma parafollicular C cells, n = 2; thyroidal C cell hyperplasia cells, n = 1; parathyroid adenoma chief cells, n = 1; pancreatic islet cell tumor islet cells, n = 1; oat cell carcinoma cell line M-103) as well as in all normal polypeptide hormone producing tissues (adrenal medulla chromaffin cells, parathyroid chief cells, thyroid parafollicular C cells, pancreatic islet cells, gut enteroendocrine cells, and anterior pituitary cells). Chromogranin may have a widespread distribution in human polypeptide hormone producing tissues, and may be a useful histologic marker for peptide producing tumors.