The Wobbler mouse possesses an inherited motoneuron disease, which expresses itself primarily at cervical spinal levels and in cranial nmotor nuclei. Cell degeneration is sporatic and negligible in other motor regions of the brain (e.g., cerebellum, corpus striatum). However, enkephalin concentrations are consistently lower in the Wobbler cerebellum throughout the motoneuron disease, whereas susbtance P concentrations are significantly higher late in the disease compared with the normal phenotype littermates. The data imply that early changes in enkephalin (aslo shown for leucine enkephalin in the spinal cord and brainstem) may be important to the etiology of the Wobbler disorder. Like the late increase of substance P, this may reflect a yet-to-be discribed response to parent cell degeneration in the raphe nuclei. TRH remained unchanged in Wobbler cerebellum and corpus striatum, wherein the other peptides studied herein also maintained similar concentrations to the normal phenotype littermates. Copyright © 1992 Published by Elsevier B.V.