Injury to a peripheral nerve due to a drug injection is of particular concern, because of both its clinical and medicolegal implications. Among numerous agents, local anesthetic solutions are most frequently injected near the main nerve trunks. In spite of the low incidence of nerve fiber injury associated with these local anesthetic agents, there are several clinical reports of injury. The author experimentally induced injection injury into the rat sciatic nerve with 2% lidocaine HCL and 0.5% bupivacaine. The neurotoxicity of these agents to the peripheral nerve was observed by light and electron microscope. The results are as follows: 1) Some inflammatory round cells and vasodilation were observed in the surrounding loose areolar tissues immediately after injection. No fibroblast or fibrosis was observed on light and electron microscopic examinations. 2) Immediately after injection, the axons were seperated by the splitting of the collagen fibers between the axons. But within one week, the collagen fibers were reunited and compacted. 3) Most cytoplasmic organelles of the axon, including the microtubules and micro filaments, were quite normal and were not altered by injection injury. But the shape of the axon was changed and shrinked to create a large space from the myelin sheath. The above change returned to normal within one week. 4) The Schwann cells, maintained the normal structure of their cytoplasm and nucleus, but some Schwann cells were seperated from the axons, and floated in the collagen tissue. They were reunited with the axons within one week. 5) There were no significant histologic differences between lidocaine and bupivacaine. 6) The above changes were easily reversible and not severe enough to interfere with nerve function permanently. In conclusion, local injection of these agents is very safe to the peripheral nerve.