The regional distribution of FLFQPQRFamide binding sites on fresh unfixed cryostate sections from post mortem specimens of human spinal cord and lower medulla oblongata was studied by quantitative autoradiographic methods using [125I]YLFQPQRFamide as ligand. Samples were taken from five cases who had died with no history of neurological disease at ages ranging from 5 months to 66 years. The biochemical and pharmacological characteristics of [125I]YLFQPQRFamide binding to mounted tissue sections were comparable to those reported for the rat in a previous study. [125I]YLFQPQRFamide appeared to interact reversibly with high affinity binding sites (Kd = 0.06 nM), distinct from opiate receptors. Sites labelled with [125I]YLFQPQRFamide were distributed unevenly within the human spinal cord and lower medulla oblongata, with the highest density in the superficial layers of the dorsal horn and the spinal trigeminal nucleus. Although moderate labelling was observed in the ventral part of spinal grey matter, dense labelling appeared in the gracile and cuneate nuclei. No binding sites were detected in white matter. These results show that, as in the rat, FLFQPQRFamide receptors in the human spinal cord and lower medulla oblongata, are mainly concentrated within spinal areas implicated in the analgesic action of opiates. The possible role of these receptors in modulating spinal nociceptive information is discussed with respect to the pharmacological effects of substances acting on FLFQPQRFamide receptors in animals.