Glutamate and related molecules are the major excitatory neurotransmitters in the central nervous system, and their receptors have been localized therein. Little is, however, known about them in the peripheral nervous system. The present study investigated the localization of glutamate receptor subunits of the alpha-amino-3-hydroxy- 5-methyl-4-isoxazolepropionate (AMPA) type (GluR1, GluR2-3, and GluR4) in the pancreas of newborn guinea pigs. With a double-labeling method of immunofluorescence and immuno-tetrahydrochloride reaction, GluR1 and GluR4 immunoreactivities were localized mostly in the insulin-secreting cells in the central mass of the islet, and GluR2-3 immunoreactivity in the peripheral rim of the islet, which consists mainly of non-insulin-secreting islet cells. With a double-labeling method employing immunofluorescence and NADPH-diaphorase (NADPH-d) histochemistry, GluR2-3 and GluR4 immunoreactivities were localized in most of the NADPH-d positive pancreatic ganglion cells. None of the NADPH-d-positive ganglion cells showed GluR1 immunoreactivity. In fact, GluR1 immunoreactivity was not detected in any of the pancreatic ganglion cells. The results indicate that glutamate is likely to exert its effects on the pancreas by activating different AMPA receptor subunits located in endocrine cells and intrapancreatic ganglia.