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Schwann cells are involved in all types of degenerative disorders of the peripheral nervous system, whether the primary lesion involves demyelination and remyelination, axonal degeneration and regeneration, or neuronal loss. The sequence of cellular changes in PNS disorders has been studied by examining the response of Schwann cells to loss and acquisition of axonal contact during Wallerian degeneration and nerve-fiber regeneration in the distal stumps of transected cat tibial nerves. Myelinating Schwann cells in distal stumps respond to axon degeneration by discarding and/or degrading their myelin sheaths, undergoing mitosis and adopting a quiescent state in which myelin-specific protein synthesis is suppressed. Myelin repair is activated by reassociation with regenerating axons destined to become myelinated: Schwann cells respond by undergoing cell division, expressing myelin-specific protein synthesis and elaborating a myelin sheath within a newly formed tube of basal lamina. The nature of the signalling mechanism from neuron to Schwann cell is unknown, although the interaction of specific ligands on the external surfaces of axon and Schwann cell is an attractive hypothesis. Since generally available methods have been developed to obtain fractions enriched in either the axolemma of myelinated fibers or the plasmalemma of quiescent Schwann cells free of neuronal regulation, the putative interactive properties of these surface membranes can now be explored.