The route and three dimensional distribution of nerve terminals in the submandibular gland were investigated in rats using immunohistochemistry for the protein gene product (PGP) 9.5, as a marker of neuronal elements. Thick fiber bundles were found along the wall of the excretory duct. Many fine fibers from these thick bundles were distributed each lobule of the submandibular gland. A large number of single fibers terminated in the area around the striated, intercalated ducts and the acini. The densities of PGP 9.5 immunoreactive terminals were measured by a computer aided analysis system in the three areas: the striated duct, the intercalated duct, and the acini, whose densities (microm/microm2) were 0.23, 0.39 and 0.05 respectively. The relatively high density of nerve terminals in the intercalated duct suggests that the duct system probably plays an unexpectedly important role in the functional aspects.