The intravenous administration of pentagastrin (0.05 and 0.5 μg/kg) to two patients with metastatic medullary carcinoma of the thyroid was followed by a very rapid two- to tenfold rise in serum levels of immuno-assayable thyrocalcitonin (TCT). The administration of calcium, either orally or intravenously, produced rises in TCT that were slower and of much smaller magnitude. Oral calcium appeared to stimulate TCT secretion in these patients without producing a rise in serum calcium levels. The data are consistent with the hypothesis that gastrointestinal hormones may influence secretion of TCT in man.