Terminal Schwann cells overlying the neuromuscular junction sprout elaborate processes upon muscle denervation. We show here that motor axons use these processes as guides/substrates during regeneration; in so doing, they escape the confines of endplates and grow between endplates to generate polyneuronal innervation. We also show that Schwann cells in the nerve provide similar guidance. Axons extend from the cut end of a nerve in association with Schwann cell processes and appear to navigate along them. The processes extend from axotomized nerves at the same rate and in the same manner as they do from axon-containing nerves. The rate of process extension limits the rate at which axons regenerate. Thus, Schwann cell processes lead and guide peripheral regeneration.