The location of methionine enkephalin neurons in the medulla oblongata that project to the dorsolateral pontine tegmentum was investigated using anterograde and retrograde tract tracing combined with immunocytochemical neurotransmitter identification. The results of these experiments demonstrate that enkephalinergic neurons from areas known to modulate nociception project to the region of the A7 catecholamine cell group in the dorsolateral pontine tegmentum. The medullary nuclei that contain these enkephalinergic neurons include the nucleus raphe magnus and the nucleus reticularis gigantocellularis pars α in the ventromedial medulla. While some of these enkephalinergic axons appose the somata and dendrites of A7 neurons, the majority of these axons appear to contact non-catecholamine neurons in the dorsolateral pontine tegmentum. Unidentified neurons located in the nucleus raphe magnus, the nucleus reticularis gigantocellularis pars α, and the nucleus reticularis gigantocellularis also project to the A7 area. Many of the neurons in the nucleus reticularis gigantocellularis pars α appear to contact both noradrenergic A7 neurons and non-catecholamine neurons in the dorsolateral pontine tegmentum, whereas most of those in the nucleus raphe magnus appear to contact non-catecholamine neurons. The anatomical findings described in this report and the results of preliminary behavioral studies provide evidence to support a model in which activation of the enkephalin-containing neurons in the ventromedial medulla facilitates nociception, while the non-enkephalin neurons mediate part of the antinociception produced by stimulating sites in the ventromedial medulla.