BACKGROUND: Intrathecal baclofen has an analgesic effect. However, the analgesic effect and neurotoxicity of epidural baclofen has not been reported. METHODS: Twenty rabbits, weighing 2.5-3.0 kg, were randomly assigned to three groups; five rabbits receiving 0.9% saline (S), five rabbits receiving 0.1 mg morphine (M), ten rabbits receiving 0.5% baclofen (B). An epidural catheter was inserted at the L(6-7) interspace, and 0.6 ml of saline, morphine or baclofen was injected. Motor and sensory deficits were measured. After two weeks, a spinal cord segment 3 cm on each side of the catheter tip was removed for histological examination. RESULTS: In the M and B groups, no rabbits showed any response of the hindlimbs to the pinch toe test. On light microscopy findings, no inflammation of the meninges or degenerative myelopathy was observed in the S or M groups. In the B group, one rabbit showed local myelopathy of the white matter, and degenerative myelopathy of white and grey matter in the area adjacent to the epidural catheter. However, these changes are focal and minimal, and thought to be ischemic changes due to vascular damage caused by catheterization. Electron microscopy findings showed no morphologic difference between the S and B groups. CONCLUSIONS: Epidural 0.5% baclofen produced antinociceptive effect with slight motor weakness. No definite neurotoxicity was observed after a single epidural injection of 0.5% baclofen in the rabbit.