IMMUNOHISTOCHEMICAL evidence is provided for (i) the occurrence of a primary sensory neuronal population immunoreactive to methionine- and leucine-enkephalin (EK) in the human trigeminal ganglion; (ii) colocalization of EK and substance P (SP) in a subpopulation of ganglion neurones and in nerve fibres and terminal-like structures in the human trigeminal spinal nucleus. The results obtained indicate that part of the EK-positive innervation of the spinal nucleus may be of ganglionic origin and raise the possibility that EK and SP are costored in and coreleased from primary afferent terminals, thus adding to the complexity of the sites and ways of interaction between these neuropeptides in the processing of sensory information.