Background: Recently, a progressive pelvic limb ataxia and paraparesis leading invariably to recumbency has been reported in Rouge-des-pre´s calves. Objectives: To characterize the clinical and pathological findings of this newly reported disease and to investigate its potential causes. Animals: Nine calves from 7 different farms were prospectively studied from initial diagnosis through postmortem examination. Methods: Physical and neurological examinations, blood tests, cerebrospinal fluid (CSF) analysis, and myelographic examinations were performed. Neuropathology was carried out on both central and peripheral nervous systems. Copper deficiency and organophosphate intoxication also were investigated. Pedigrees were analyzed. Results: Age of onset varied from 2 to 6 weeks. Initial signs included pelvic limb ataxia and paraparesis. The neurological signs systematically progressed, over a 1–3-month period, to severe pelvic limb and truncal ataxia along with moderate paraparesis, leading to permanent recumbency. Animals remained alert. Cranial nerve function was normal. Muscle atrophy was not observed and spinal reflexes were normal. Blood tests, CSF analysis, and myelographic examination did not identify any abnormality. Neuropathology indicated neuronal fiber degeneration particularly in the dorsolateral and ventromedial funiculi of the spinal cord and in the peripheral nerves. Degenerative lesions also were observed in lateral vestibular and thoracic nuclei. No environmental factors such as copper deficiency or organophosphate intoxication could be incriminated as the cause of this axonopathy. Pedigree analysis suggested an inherited defect. Conclusions and Clinical Importance: The first description of a central and peripheral axonopathy is reported in Rougedes- pre´s calves. An inherited defect is highly suspected.