We report the case of an 11-year-old male who developed subacute diffuse polyradiculoneuropathy, associated with digestive symptoms and Epstein-Barr virus infection. Parental consanguinity was present. The laboratory findings including bone marrow smear were consistent with hemophagocytic lymphohistiocytosis (HLH). Electrophysiological study of peripheral nerves revealed an intense and diffuse demyelinating process. The histological nerve lesions were severe and purely demyelinating. Most axons were intact. There was a diffuse infiltration of the nerve parenchyma by mononuclear cells. Immuno-electron microscopic study evidenced entry of macrophages into Schwann cell cytoplasm with dissociation of myelin sheaths. This boy died several months after the onset of the neuropathic symptoms. HLH is a rare genetic or acquired disorder in childhood characterized by abnormal immune activation, which induces an uncontrolled inflammatory response with sustained hyperactivation of T lymphocytes and macrophages. Only very rare cases of peripheral nerve involvement have been described in HLH. This is the first case showing that peripheral nerves, as other viscera, may be destroyed by the macrophagic infiltration, which characterizes HLH.