The present study was undertaken to analyze the expression of two opioid receptor genes (mu and kappa) in different gastrointestinal regions of the rat. A combination of mRNA quantification and immunohistochemical visualization was used to characterize their expression. Using naive animals, RNA was extracted from tissues and used in RNase protection assays: both receptor mRNAs were expressed in all investigated areas but displayed different expression profiles across the various regions of the digestive tract. Stomach and proximal colon appeared to have the highest expression levels of both receptors, whereas the lowest expression levels were found in the duodenum. Expression levels for both receptors were always lower in the gastrointestinal tract compared to the brain. However, the kappa-receptor expression in the proximal colon represented 40% of the amount found in the brain, which is almost 4 times as high as the respective mu-receptor expression. In contrast to smooth muscle cells, myenteric plexus perikarya of the rat stomach and colon were immunoreactive with antibodies raised against the C-termini of both kappa- and mu-opioid receptors. Numerous nerve fibers were also immunoreactive for both mu- and kappa-receptors and distributed in the longitudinal and circular muscle layers. Small perikarya immunoreactive for mu-receptor were localized around the myenteric plexus and at the submucosal border of the circular muscle, whereas only few perikarya were immunoreactive for the kappa-receptor. We conclude that at least in rat stomach and colon, mu- and kappa-opioid receptors may directly control neuronal communication but seem to have no direct influence on smooth muscle cells.