We studied clinical, electrophysiologic, and nerve biopsy findings in two men with evidence of severe central and peripheral demyelinating disease. These patients may be rare examples of MS with associated severe, chronic, clinically evident peripheral demyelinating neuropathy. Alternatively, they may be cases of some other form of combined central-peripheral myelinopathy or fortuitous coincidence of MS with idiopathic inflammatory-demyelinating neuropathy. There have been only five other reports of clinically evident combined central-peripheral myelinopathy, but there have also been reports of only electrophysiologic or nerve biopsy evidence (without clinical manifestation) of peripheral neuropathy in MS patients.