An ascending impairment of tail nociception is a previously undescribed clinical sign of acute experimental allergic encephalomyelitis (EAE) in the rat. It occurs in EAE induced by inoculation with purified central nervous system (CNS) myelin basic protein (MBP) as well as with whole spinal cord. It is invariably present and consists of an absence of the vocalization response to noxious mechanical stimulation of the tail. This impairment of nociception evolves over 1-3 days, simultaneously with the development of tail weakness, and resolves more rapidly than the tail weakness. Light-microscopic, electron-microscopic and electrophysiological studies indicate that it is due to demyelination-induced conduction block in the small diameter myelinated afferent (A delta) fibres in the sacral and coccygeal dorsal root ganglia, dorsal roots and dorsal root entry zones. Unmyelinated fibres appear to be largely spared.