West Nile virus can cause a febrile illness that may progress to meningoencephalitis. The only available treatments are ribavirin (although it has had limited success in humans) and interferon alpha-2b. A small pilot study showed that starting treatment with interferon alpha-2b on days 1-4 of hospital admission may reduce disease severity and complications. We encountered an 83-year-old man with West Nile meningoencephalitis who began taking interferon alpha-2b 3 weeks after disease presentation. Although studies and reports indicate that treatment is less likely to provide a favorable response if administered after days 1-6 of the disease course, the patient experienced substantial beneficial effects from this treatment. This is the first case report, to our knowledge, that describes successful treatment with interferon alpha-2b after several weeks of West Nile virus infection. Further studies are warranted to more fully understand the value of interferon alpha-2b in treating West Nile meningoencephalitis.