We studied the effect of electrical stimulation of the vagus nerves and the effect of vasoactive intestinal polypeptide (VIP) on the secretion of pancreatic spasmolytic polypeptide (PSP) from isolated perfused porcine pancreas. We measured the concentration of PSP in the pancreatic juice and in the venous effluent by radioimmunoassay. The concentration in the pancreatic juice varied between 1 and 180 µg/ml, and in the venous effluent between 1 and 10 ng/ml. PSP is thus mainly an exocrine product. However, the concentrations in juice and venous effluent varied in parallel. Electrical vagus stimulation increased the output in the juice of PSP approximately 30 times. Atropine (10-6M) prevented the increase in PSP concentration during vagus stimulation, but only partially inhibited the output. VIP (10-8M) increased the output of PSP but decreased the concentration. We conclude from these results that PSP secretion is controlled by neural parasympathetic mechanisms that include both cholinergic and peptidergic pathways.