Using an indirect immunoperoxidase technique, we studied the distribution of immunoreactive fibers and cell bodies containing methionine-enkephalin- Arg 6-Gly 7-Leu 8 in the adult human brainstem. Immunoreactive cell bodies were found in the reticular formation of the medulla oblongata (in which we observed the highest density of immunoreactive cell bodies) and the pons, the solitary nucleus, the hypoglossal nucleus, the medial and spinal vestibular nuclei, the lateral cuneate nucleus, the nucleus prepositus, the central gray of the pons and mesencephalon, the central and pericentral nuclei of the inferior colliculus, the superior colliculus, ventral to the superior olive and in the midline region of the pons and mesencephalon. The highest density of immunoreactive fibers containing methionine-enkephalin- Arg 6-Gly 7-Leu 8 was found in the spinal trigeminal nucleus, the central gray and the reticular formation of the medulla oblongata, pons and mesencephalon, the solitary nucleus, the spinal vestibular nucleus, the dorsal accessory olivary nucleus, the raphe obscurus, the substantia nigra and in the interpeduncular nucleus. The widespread distribution of immunoreactive structures containing methionine-enkephalin-Arg 6-Gly 7-Leu 8 in the human brainstem indicates that this neuropeptide might be involved in several physiological mechanisms, acting as a neurotransmitter and/or neuromodulator. © 2004 IBRO. Published by Elsevier Ltd. All rights reserved.