Extensive peripheral nerve injuries can result in the effective paralysis of the entire limb or distal portions of the limb. The major determinant of functional recovery after lesions in the peripheral nervous system is the accurate regeneration of axons to their original target end-organs. We used the mouse femoral nerve as a model to study motor neuron regeneration accuracy in terms of regenerating motor neurons projecting to their original terminal pathway to quadriceps muscle vs. the inappropriate pathway to skin. Using a variety of surgical manipulations and the selective removal of Schwann cells in the distal nerve via molecular targeting, we have examined the respective roles of end-organ influence (muscle) vs. Schwann cells in this model system. We found evidence of a hierarchy of trophic support that regulates motor neuron regeneration accuracy with muscle contact being the most potent, followed by the number or density of Schwann cells in the distal nerve branches. Manipulating the relative levels of these sources of influence resulted in predictable projection patterns of motor neurons into the terminal pathway either to skin or to muscle.