This paper reviews the anatomical evidence for the presence of glutamate (GLU) in noradrenergic neurons of the nucleus locus coeruleus (LC) and adjacent nuclei in the dorsolateral pontine tegmentum (DLPT) that project to the spinal cord, cerebellum, or cerebral cortex. Additionally, the evidence for the existence of methionine-enkephalin (ENK) in noradrenergic neurons of the DLPT that project to the spinal cord of the cat is reviewed. In these studies, we have combined the retrograde transport of either Fast Blue (FB), rhodamine labeled latex microspheres (MS), or rhodamine labeled dextran and indirect immunofluorescence histochemistry to determine whether the neurons that contain tyrosine hydroxylase (TH) and project to these terminal fields also contain GLU or ENK. The neurons of the cat that project to the spinal cord, cerebellum, and neocortex were observed in the nucleus LC and Kolliker-Fuse (KF) nucleus. They were also present, to a lesser extent, in the nucleus subcoeruleus (SC) and nuclei parabrachialis medialis (PBM) and lateralis (PBL). In the rat the majority of the neurons that project to the neocortex and hippocampus were located in the nucleus LC. Our data revealed a major proportion of these neurons to be immunostained for both GLU and TH (cat, rat), or ENK and TH (cat). Functional implications of such colocalized neurochemicals within individual LC projection neurons are discussed.