We studied the effect of electrical stimulation of the vagus nerves on the exocrine secretion of isolated perfused porcine pancreas before and after procedures that almost completely blocked the effects elicited by infusions of gastrin-releasing peptide (GRP): desensitization of the pancreas for GRP (by perfusion with high concentrations of GRP); administration of an antagonist of GRP action [D-Arg1, D-PrO2, D-Trp7,9, Leu11)-substance PI; and perfusion with Fab fragments of antibodies against GRP. Both desensitization and antagonist administration significantly (p < 0.01) inhibited the effect of vagus stimulation on pancreatic protein secretion (by 42.1 and 33%). The inhibitory effect of anti-GRP perfusion was less pronounced (22% inhibition, 0.05 >p < 0.1). The results support the notion that pancreatic, GRP-producing nerve fibers are involved in the neural control of pancreatic enzyme secretion.