Gastroenteropancreatic human neuroendocrine (NE) cells (normal and neoplastic) were investigated for the expression of the neuroendocrine-specific polypeptides synaptophysin, chromogranin A, secretogranin I (chromogranin B), and secretogranin II, using immunohistochemistry and immunoblotting. Monoclonal antibody against synaptophysin stained most, and possibly all, of the neuroendocrine cells in both normal and neoplastic tissue. Monoclonal antibody against chromogranin A also stained a high proportion of normal and neoplastic neuroendocrine cells. Immunostaining with polyclonal antisecretogranin I and antisecretogranin II antibodies was detectable in almost all of the normal and neoplastic tissue sections that were analyzed, and it was confined to a smaller population of neuroendocrine cells than that observed for synaptophysin and chromogranin A. Consistent with the immunohistochemical observations, immunoblotting revealed the presence of all four antigens in various tumors. The data show that synaptophysin and chromogranin A, for which monoclonal antibodies are commercially available, may be used as diagnostic markers for human gastroenteropancreatic tumors. Our results also suggest that the development of monoclonal antibodies against human secretogranins I and II will provide additional tools for a refined diagnosis of such tumors.