A 42-year-old man was diagnosed with large cell non-Hodgkin's lymphoma 3 years after autologous bone marrow transplantation for Hodgkin's disease. The day before beginning systemic chemotherapy, the patient began to have symptoms of a sensorimotor neuropathy characterized by proximal and distal weakness, lower-extremity areflexia, elevated cerebrospinal fluid protein level, and evidence of demyelination on nerve conduction studies. Symptoms progressed despite two courses of intrathecal methotrexate, for possible lymphomatous meningitis, as well as systemic chemotherapy. The diagnosis of chronic inflammatory demyelinating polyneuropathy was made. Daily plasma exchange was performed for a total of 10 treatments with immediate improvement and eventual complete recovery in strength, sensation, and gait. A review of the literature confirms that inflammatory demyelinating polyneuropathy is a highly unusual but important cause of peripheral nervous system dysfunction. The potential for complete response to plasma exchange should be recognized in patients with symptoms, signs, and nerve conduction studies suggestive of chronic inflammatory demyelinating polyneuropathy.