Controversy still surrounds the differential susceptibility of nerve fibers to local anesthetic conduction block. In order to help resolve this controversy, we developed anin vivomodel of peripheral nerve blockade in the cat that closely reproduced the clinical state. Using this model, differential rate of nerve blockade of A-alpha, A-delta, and C fibers by 2-chloroprocaine, lidocaine, bupivacaine, and etidocaine was observed and quantitated. C fibers were blocked first by 2-chloroprocaine, lidocaine and bupivacaine. Etidocaine blocked A-delta fibers first. A-alpha fibers always were blocked last. Of the four local anesthetics tested, 2-chloroprocaine produced the greatest differential rate of block of the nerve fibers, and etidocaine produced the least.