We have examined the effect of acrolein, an aldehyde product of lipid peroxidation, on axons in isolated guinea-pig spinal cord white matter. We found that 200 microM acrolein, but not 50 microM, induced a time-dependent loss of compound action potential conduction. Such conduction loss was irreversible within 1 h after acrolein perfusion. Parallel anatomical assessment indicates membrane integrity breakdown based on a horseradish peroxidase-exclusion assay. This is the first report to suggest that acrolein inflicts severe axonal damage. Since axonal damage within white matter plays a key role in the pathology of traumatic spinal cord injury, we suggest that acrolein may be a critical factor in mediating secondary functional loss.