['Highly concentrated lidocaine has been reported to induce irreversible loss of membrane potential in crayfish nerve, which implies membrane disruption as one of the direct mechanisms of lidocaine-induced neurotoxicity. To confirm lidocaine-induced membrane disruption in mammalian nerve, a lactate dehydrogenase (LDH) leakage from rat sciatic nerve was measured in vitro. Before applying lidocaine, the desheathed nerve was incubated for 60 min in Krebs-Ringer solution at 37 degrees C to examine basal LDH activity. It was then incubated in 80 mM lidocaine solution at pH 7.3 for 15, 30, 60, or 120 min. Other nerves were immersed in 800 mM choline solution for 120 min. Total LDH activity per wet weight of nerve tissue was assayed using spectrophotometry. It was also determined using nerves cut into 10 segments and incubated in distilled water for 60 min. The LDH activity in the lidocaine group showed a time-dependent increase. After the 60- and 120-min incubation with lidocaine, the amount of LDH activity was significantly increased compared with the choline group and was similar to that of the group incubated in distilled water. We conclude that 80 mM lidocaine may be sufficient to cause membrane damage and facilitate the leakage of enzymes from cytoplasm.'] Does lidocaine disrupt axonal membrane of rat sciatic nerve in vitro?