A 54-year-old man with chronic B hepatitis was treated with interferon alfa. Despite resolution of the hepatitis B viral infection, he experienced severe jaundice, ascites, and encephalopathy. Further work-up showed hyperglobulinemia, chiefly immunoglobulin G, and positive smooth muscle and anti-nuclear antibodies. Because of these "autoimmune" features, the patient was treated with prednisone. One month later, a significant clinical and biochemical improvement was observed. A possible autoimmune mechanism induced by interferon alfa is proposed as the cause for the perpetuation of the necroinflammatory activity.