Chronic renal failure is associated with structural and functional abnormalities of the exocrine system of the pancreas. Certain data suggest that the excess parathyroid hormone (PTH) in these patients may participate in the genesis of these pancreatic derangements. However, direct evidence that PTH exerts a direct effect on the exocrine pancreatic system is not well documented. The present study examined the effects of the intact molecule (1-84 PTH) and of the amino-terminal fragment (1-34 PTH) of the hormone on the basal output of pure pancreatic juice (PPJ) volume and pancreatic protein secretion in the rat. 1-84 PTH but not 1-34 PTH significantly (p less than 0.01) stimulated the output of PPJ volume without an effect on protein secretion. The magnitude of this stimulatory effect of 1-84 PTH depended on the dose of the hormone administered, and it was related to its biological activity, since inactivation of PTH abolished its action on the output of PPJ volume. The simultaneous administration of the calcium channel blocker, verapamil, reduced but did not abolish the stimulatory effect of PTH on the volume of PPJ output. The data demonstrate that: (1) the ductal cells of the pancreatic acini are targets for PTH and (2) the action of the hormone on these cells is mediated, at least in part, via PTH-induced entry of calcium into the target cells.