Two cases of leflunomide-induced peripheral neuropathy are described; in a 60-year-old woman with sero-negative polyarthralgia-myalgia syndrome and a 65-year-old man with sero-negative rheumatoid arthritis, both treated with leflunomide at 20 mg/day. Nerve conduction studies and electromyogram showed sensorimotor axonal neuropathy in both cases. An alternative cause for the axonal neuropathy was excluded by extensive investigations, including cerebrospinal fluid examination and nerve biopsy in the second patient. Both patients stabilized symptomatically and electrophysiologically upon cessation of leflunomide. It is possible that leflunomide-induced peripheral neuropathy has been under-reported and under-recognized. (c) 2006 Elsevier Ltd. All rights reserved.