Existing methods for the histochemical demonstration of gastrointestinal cells are somewhat limited. Chromogranin represents a family of proteins that coexist with catecholamines in the secretory vesicles of adrenal medulla cells. In the present study, immunocytochemistry was used to test whether chromogranin is a marker for gut endocrine cells. Serial sections of each area of human gut were immunostained for chromogranin and for the amine and each of the peptides known to be present in mucosal endocrine cells. Chromogranin was immunostained in large numbers of endocrine cells in all tissues examined. All identified endocrine cell types were found, in serial sections or by sequential silver impregnations, to be chromogranin immunoreactive. However, the possibility exists that some chromogranin-immunoreactive cells contain a yet to be discovered endocrine substance. Immunostaining of chromogranin thus appears to provide a means for demonstrating all gastrointestinal mucosal endocrine cells identifiable by the methods described in this study.