In order to better understand the regulation of blood flow to tooth-related structures, the patterns of VIP- and NPY-ergic innervations in the rat were examined. Nerve fibers showing NPY-like immunoreactivity (NPY-LI) frequently occurred in the walls of the large main arteries, as well as in association with the arterioles, to a high degree co-existing with tyrosine hydroxylase (TH), whereas VIP-LI was mainly restricted to the walls of the large arteries. After sympathectomy, no NPY/TH-LI nerve fibers were seen in blood vessel walls. However, a NPY-immunoreactive nerve population remained in the walls of the large arteries, NPY- and VIP-LI co-existing in this nerve population. Both immunoreactions were intense. The present study suggests that a NPY/sympathetic innervation as well as a VIP innervation (large arteries) are likely to have substantial roles in the balance and maintenance of vasoregulation in tooth-related structures and that a NPY/VIP innervation becomes of particular importance when the NPY/sympathetic innervation is destroyed.