The aim of the present study was to evaluate the effect of calcitonin on insulin response to intravenous arginine in normal humans. For this purpose, eight normal subjects were submitted to an iv arginine tolerance test twice, under basal conditions and during the simultaneous infusion of calcitonin plus arginine. Calcitonin caused a clear inhibition of the insulin response to arginine (p less than 0.01) and also exaggerated the rise in plasma glucose seen with iv arginine (p less than 0.01). Theophylline (250 mg as iv bolus, followed by an iv infusion of 500 mg/h) failed to overcome the inhibitory effect of calcitonin on insulin secretion. It is hypothesized that calcitonin inhibits insulin secretion by changing calcium distribution in the pancreatic beta-cell.