Neuropathic pain is often a difficult condition to treat. Clinical and laboratory studies using intravenously administered local anesthetics or antiarrhythmic agents support the use of these drugs for the treatment of neuropathic pain. The availability of the oral antiarrhythmic medication, mexiletine, has made it possible to study the effects of an orally administered medication on chronic neuropathic pain. The study used a double-blind placebo-controlled design to examine 11 subjects in whom treatment with conventional pain medications had been unsuccessful. Subjects had a history of peripheral nerve injury or dysfunction, and all complained of symptoms consistent with neuropathic pain. After baseline pain measurements, mexiletine or placebo was given in gradually increasing doses to a maximum daily dose of 750 mg mexiletine. After 1 month at steady state, the subject received the alternative medication. Mexiletine was found to produce a statistically significant reduction in reported pain when compared to baseline or placebo. Pain scores were rated on a scale from 0 (no pain) to 10 (unbearable pain). Median pain scores prior to mexiletine were 7, after placebo treatment 7, and while receiving mexiletine (750 mg/day) 4. Side effects were mild and well-tolerated. Mexiletine may be effective in reducing neuropathic pain for patients in whom alternative pain medications have been unsatisfactory.