The localization of methionine-enkephalin-Arg6-Gly7-Leu8 (Met-Enk-Arg-Gly-Leu)-like immunoreactivity in the medullospinal liquor-contacting neurons (LCNs) of the rat was immunohistochemically investigated using a modified Sternberger's PAP method. In this study, we also examined the distribution of Met-Enk-Arg-Gly-Leu-like immunoreactive LCNs in the entire length of the medulla oblongata and spinal cord. The immunoreactive LCN possessed an oval, polygonal or rod-shaped perikaryon which protruded an axon-like process and a CSF-contacting process. In the entire length of the medulla oblongata and spinal cord, 60-70 immunoreactive LCNs were observed. They were sparsely distributed along the central canal. The ratio of the number of immunoreactive LCNs in each segment/total number of immunoreactive LCNs in the medulla oblongata and whole spinal cord was as follows: medulla oblongata, 0%; cervical segments, 28.1%; thoracic segments, 56.8%; lumbar segments, 12.0%; sacral segments, 3.0%; and coccygeal segments, 0%. When the immunoreactivity of perikarya of LCNs was weak, a few nerve terminals with a strong Met-Enk-Arg-Gly-Leu-like immunoreactivity were noticed on them. These findings suggest that preproenkephalin A-related opioid peptides including Met-Enk-Arg-Gly-Leu may be secreted into the cerebrospinal fluid (CSF) through the terminal portions of axon-like processes and/or CSF-contacting processes of LCNs. Enkephalin-containing nerve terminals on the LCNs may represent modulating afferents aiding the receptive and/or secretory functions of the neurons.