The influence of synthetic salmon calcitonin (CT) on paraphysiological endocrine pancreas was investigated in Man. Large dose (100 U) as well as low dose (1 U) of CT inhibits glucose-induced insulin responses, reduces the suppressive effect of glucose on glucagon secretion and impairs glucose tolerance. These effects are not mediated by hypocalcemia. Studies in which theophylline or calcium were infused in addition to CT suggest that the mode of action of CT is mediated via a change in calcium redistribution in the islet cells. The diabetogenic action of CT is not observed in Paget and osteoporotic patients, after prolonged administration of the hormone.