We treated four cases of acute unresolving non-A, non-B hepatitis, and eleven cases of chronic non-A, non-B hepatitis with recombinant interferon alpha-2a for up to one year. The dose of interferon was initially 3 million units daily, and was gradually decreased to 1 million units three times weekly. The overall response rate was 80 percent (twelve out of fifteen cases) at the end of treatment. Relapse occurred after the cessation of treatment in seven of the eight cases of chronic disease responding to interferon therapy. In contrast, three of the four cases of acute unresolving hepatitis became (sero)negative for antibody to hepatitis C virus, and in three completely normal serum aminotransferase levels persisted for more than one year after therapy. It is urged that early recognition of non-A, non-B hepatitis should be striven for, because interferon therapy may lead to an improved prognosis of the disease, particularly in cases of possible transitional phase from acute to chronic disease.