Many studies have shown that in normal man salmon and porcine CT administration in bolus inhibits the release of TSH, LH, GH, and glucose- or arginine-induced insulin secretion. In the present study we investigated the effects of human synthetic calcitonin (hCT) on glucose- or arginine-induced insulin secretion in man. Twenty-two subjects were submitted to i.v. administration of hCT during glucose or arginine test. In our opinion, the most interesting results are those observed with arginine plus hCT at two different dosages (25 micrograms and 12.5 micrograms infused in 30 min). In fact arginine plus hCT (25 micrograms in 30 min) administration induced a significant increase of glycemia at 5, 10 and 20 min (p less than 0.01) and at 30 min (p less than 0.05) and a significant decrease of IRI at 5, 10, 20 and 30 min (p less than 0.001) and at 45 min (p less than 0.005). The highest plasma CT levels were observed at 15 and 30 min (490 and 540 pg X ml-1). Arginine plus hCT (12.5 micrograms in 30 min) infusion induced a similar significant increase in plasma glucose at 10, and 20 min (p less than 0.05) and at 30 min (p less than 0.01) and a significant decrease of plasma IRI at 10 min (p less than 0.05) at 20 min and 30 min (p less than 0.005). The highest plasma CT levels were reached at 20 min and 30 min (250 and 270 pg X ml-1, respectively). Our results clearly demonstrate that physiologic doses of hCT are able to inhibit arginine induced insulin secretion in normal man. Since insulin induces hypercalcemia and food ingestion increases both insulin and CT, one could hypothesize that CT inhibits insulin secretion thus controlling post-prandial hypercalcemia by its osteotrophic effect and by its action upon calcium redistributed within the cells.