The secretion of various pancreatic hormones (insulin, glucagon and pancreatic polypeptide) is affected to a different extent by the cholinergic system. In 7 healthy subjects the effects of treatment for 1 week with pirenzepine, an anticholinergic drug selective for muscarinic receptors, on basal secretion of these hormones and on that induced by i.v. glucose (IVGTT) and arginine were evaluated. The drug did not reduce basal levels of insulin and glucagon whereas it caused an appreciable reduction in basal pancreatic polypeptide (PP). The responses of insulin and blood glucose to IVGTT and to arginine were not changed by treatment, nor was that of plasma glucagon to arginine. The infusion of arginine did induce an increase in PP level, which reached a statistically significant maximum at 90 min. This response was not particularly different after administration of pirenzepine. Thus, the results confirm the finding that arginine stimulates PP secretion in vivo and that pirenzepine reduces the basal level of the hormone, whereas it did not appear to affect the response to arginine. The findings exclude any direct action of the drug on insulin or glucagon secretion or on glucose metabolism in general.