A patient with acute hepatitis B developed significant polyarthritis. After 10 months of observation he had not cleared the virus and continued to have symptomatic joint problems, with migratory polyarthralgia, tenosynovitis of the left wrist, and a large knee effusion. Hepatitis B surface antigen (HBsAg) and hepatitis B virus (HBV) DNA levels were measured in the synovial fluid and were found to be virtually identical to serum levels, indicating the potential infectivity of this fluid. The patient was treated with 14 weeks of thrice-weekly lymphoblastoid interferon and cleared all markers of viral replication. The arthritis resolved with the disappearance of measurable HBsAg. Interferon may be effective therapy for this disorder.