The prognosis of patients with progressive multifocal leukoencephalopathy is poor, with few patients showing remission or surviving. We describe a 37-year-old man who developed progressive multifocal leukoencephalopathy in association with sarcoidosis. Despite treatment with cytarabine and acyclovir, he continued to deteriorate. Shortly following the addition of interferon alfa, he made a dramatic improvement, regaining full functional independence. The use of interferon alfa in addition to cytarabine in such patients offers a new therapeutic approach worthy of further trial.