Pentagastrin stimulates the release of calcitonin from normal C-cells in the human thyroid. In the present investigation the effect of cimetidine on the liberation of calcitonin in response to intraarterial pentagastrin (0.6 micrograms . kg-1) was studied in 14 normocalcaemic patients undergoing surgery for thyroid adenomas. Cimetidine was administered as a bolus injection of 200 mg followed by an intravenous infusion of 1.5 mg . kg-1 . h-1. In seven patients not given cimetidine, mean calcitonin concentration in the thyroid vein rose from 419 +/- 58 to 2787 +/- 645 pM in response to pentagastrin. In seven patients given cimetidine, mean calcitonin concentration only increased from 107 +/- 33 to 166 +/- 51 pM after pentagastrin. The difference between the two groups was statistically significant both during basal conditions (P less than 0.001) and in response to pentagastrin (P less than 0.01). The results suggest that pentagastrin affects normal C-cells via release of histamine and that cimetidine markedly interferes with this mechanism.