Twenty pancreatic endocrine tumors and one duodenal somatostatinoma were stained with polyclonal antisera against eight hormones, neuron-specific (NSE), and with a monoclonal antibody against the endocrine granule protein chromogranin. Silver staining was performed on all tumors with the Grimelius method. All the tumors and all cells in the normal pancreatic islet showed NSE immunoreactivity. Chromogranin immunoreactivity was found predominantly in the glucagon cells of normal islets, in one glucagonoma, four gastrinomas and in 10 tumors associated with multiple hormonal production, but not in five insulinomas or in one somatostatinoma. Grimelius reactivity was identical to chromogranin immunoreactivity in all cases except that more cells in the tumors and in the normal islets were positive for chromogranin. Both chromogranin and NSE were detected in a metastasized pancreatic endocrine tumor which had metastasized to a peripancreatic lymph node. The metastatic tumor failed to stain with antisera to all eight hormones. These results indicate that chromogranin and NSE are excellent general markers for pancreatic endocrine tumors and that the Grimelius stain and other related argyrophilic reactions may involve binding to chromogranin.