Peripheral neuropathies can result from a failure to form or maintain the myelin internode or from autoimmune-mediated demyelination. Several gene defects responsible for the most common inherited human peripheral neuropathies referred to as Charcot-Marie-Tooth disease have been reported. These studies identified PMP-22 and connexin-32 as proteins that are essentiel for normal myelination. Point mutations in Po protein, PMP-22, and connexin-32 have been identified as causes of inherited peripheral neuropathies. In addition, studies indicated for the first time that alterations in PMP-22 gene dosage (trisomy and monosomy) can induce inherited peripheral neuropathies. Little is known, however, about how these gene defects cause myelin pathology. This report describes the distributions of proteins within the peripheral myelin internode and discusses how these molecules contribute to the pathogenesis of inherited and autoimmune peripheral neuropathy. A better understanding of the molecular composition of the myelin internode is essential for diagnosis and treatment of human peripheral neuropathies.