This study was undertaken because of several recent reports of adverse neurologic reactions following the use of 2-chloroprocaine. Carotid sheaths containing undisturbed vagus nerve were surgically exposed in rabbits and bathed in situ for up to 1 hour in one of the following-isotonic solutions: physiologic salt solution, lidocaine 2%, bupivacaine 0.75%, 2-chloroprocaine 3%, or a mixture of 2-chloroprocaine 1.5% and bupivacaine 0.375%. Each solution contained epinephrine, 5 micrograms/ml, (1:200,000). In other animals the carotid sheaths were bathed in physiologic salt solution, or 2-chloroprocaine 3% without epinephrine. The nerves were excised 10 to 12 days later. C-fiber impulse conduction was normal in nerves that had been exposed to physiologic salt solution with or without epinephrine, to lidocaine, or to bupivacaine. Conduction was absent or markedly impaired in several nerve specimens following exposure to 2-chloroprocaine. Histologic sections revealed the presence of epineurial cellular infiltration and fibrosis, perineurial fibrosis, and axonal degeneration in nerves that had been exposed to 2-chloroprocaine or the mixture of 2-chloroprocaine and bupivacaine. Histologic abnormalities were minor or absent following exposure to lidocaine, to bupivacaine, or to physiologic salt solution. These findings suggest that, under the conditions of the experiments, 2-chloroprocaine is more neurotoxic than lidocaine or bupivacaine.