The mechanisms of persistent differential blocks that accompany subarachnoid and epidural anesthesia are clarified here with the aid of two principles derived from in vitro study of individual myelinated axons: 1) conduction can leap two consecutive blocked nodes but not three, and 2) a fiber length with more than three consecutive nodes bathed by weak anesthetic may block by decremental conduction, the requisite concentration varying inversely with the number of nodes bathed by anesthetic. Principle 1 applies in epidural blockade, where anesthetic bathes only a few millimeters of segmental nerve extradurally in the intervertebral foramen. Here, three-node block will be rare in large, long-internode fibers but likely in small, short internode fibers, thus explaining the differential retention of motor power in the presence of block of pain, which is achieved in epidural anesthesia when relatively weak solutions are used, as in obstetrics. Principle 2 may intervene in subarachnoid blockade where, cephalad to the site of puncture, increasingly concentrated anesthetic bathes increasing lengths of fibers in the craniocaudal succession of spinal nerve roots. This will produce decremental conduction block in increasingly long internode fibers in successive roots, reflected in a corresponding craniocaudal segmental sequence of blocked physiological functions: vasoconstriction, cutaneous temperature discrimination, pinprick pain sensibility, and skeletal motor activity. The segmental spatial differential sequence migrates with time but resembles the temporal differential sequence of loss seen at the onset of peripheral nerve blocks. Several other previously disparate clinical observations follow logically from the new interpretation.