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 co-stored in and co-released 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.