Amino acid solution (50 mM tryptophan and 50 mM phenylalanine in saline) introduced into the canine duodenal loop causes an increased enzyme output from the pancreas, whereas administration of 0.1 N HCl into the duodenal loop causes an increased juice flow from the organ. Local anesthetic, lidocaine, introduced into the duodenal lumen suppressed the pancreatic enzyme releasing response to the intraluminal amino acid without affecting the juice flow response to the hydrochloric stimulus. Intravenously administered lidocaine did not block the pancreatic response to the intraluminal amino acid stimulus, suggesting that lidocaine affects the chemoreceptive, apical part of the endocrine cell or paraneuron which releases cholecystokinin-pancreozymin (CCK-PZ). Neither was the pancreas responding to an intravenous injection of CCK-PZ (5 Ivy Dog Units) suppressed by intravenously administered lidocaine even when its arterial concentration exceeded the convulsion level. This indicates that lidocaine affects the duodenal paraneurons recognizing the luminal stimuli but not the pancreatic cells responding to the hormones released by them. The results further suggest that in paraneurons as well as in neurons there seems to be a spectrum with regard to the susceptibility to anesthetics; thus the secretin releasing paraneuron is much more resistant to lidocaine than the CCK-PZ producing one.