BACKGROUND: Phenol is the most commonly used neurolytic agent for the management of intractable somatic pain, but side effects such as motor dysfunction and potential loss of bladder or rectal sphincter function develop following their application. This study observed functional changes of hind limb and neuropathologic changes in the sciatic nerve after phenol application, highlighting the time of nerve regeneration. METHODS: Functional changes in hind limbs were observed for 6 weeks and the distal part of the phenol-injected or dripped sciatic nerve was severed in 3 rats of each group respectively at 10 minutes, 1 hour, 24 hours, 3 days, 1 week, 2 weeks, 4 weeks and 6 weeks. The pathologic changes in the severed nerves were observed under the electron microscope. RESULTS: The phenol-injected or-dripped hind limbs showed more pronounced motor weakness and more obvious gait changes. About 2 weeks after the phenol application, gradual improvement of gait changes began, and after 6 weeks, motor weakness and gait changes were no longer perceptible. In the group with phenol injection, at 10 minutes after injection, destructive lesions were confined to unmyelinated fibers and the myelin sheath of small myelinated fibers. On the 3rd day and at 1 week, pathologic changes on axonal fibers and Schwann cells were in progress with phagocytosis in spite of myelin restitution. From 2 to 4 weeks, axonal regeneration and remyelination appeared concurrent with myelin disintegration and axonolysis, and histologic findings at 6 weeks were similar to those of the control group. In the group with phenol drip, the histologic changes in the sciatic nerve were very similar to the injection group. CONCLUSIONS: These results suggest that histopathologic lesions after a phenol application on the peripheral nerves are not influenced by application methods. The progress of histopathologic changes is obvious according to the time interval following the phenol application. Accordingly, side effectsthat developed following the use of phenol may be improved around the time when the nerve regeneration occurs, between the second and fourth weeks after the injection. The course of histopathologic changes and clinical findings following the application of phenol is very similar to the previous experiment using alcohol.