Biochemical and immunohistochemical analyses of the central nervous system (CNS) have been performed on the wobbler (WR) mouse, a mutant affected by a spinal atrophy. Total polypeptide patterns as well as specific neuronal and glial marker proteins were analyzed, using 2-dimensional gel electrophoresis, immunoblotting and ELISA, and the determination of enzyme activities. Despite the loss of motoneurons, the specific activities of choline acetyltransferase were not lower in WR than in control CNS samples. On the other hand, the level of glial acidic fibrillary protein (GFAP) was increased 3- to 5-fold in the spinal cord and brain stem of WR mice but not in the cerebellum. Immunohistochemistry indicated that the higher content of GFAP was due to a dense network of astrocytic processes extending over the whole cross-section of the spinal cord. This finding indicates that astrocyte overgrowth may be a fundamental feature of the wobbler disease, rather than occurring locally in response to motoneuron degeneration.