Interferon is currently considered to be the only accepted effective treatment for chronic viral hepatitis. A history of the treatment of chronic hepatitis B and C before the use of interferon is presented here. Hepatitis B virus does not seem to be directly cytopathic and the disease is known to be modulated largely by the host's immune response. Experience with immunosuppressant and immunostimulant drugs and a wide variety of antiviral agents, however, has indicated that none of these are of any benefit in patients with chronic hepatitis B, with the possible exception of adenine arabinoside. In view of the much more recent identification of the hepatitis C virus, studies of therapy for chronic hepatitis C are inevitably less extensive. A pilot study using acyclovir in patients with chronic non-A, non-B hepatitis did not show any benefit, although the treatment period may have been too short for the results to be conclusive. The only agent other than alpha interferon to be tried in chronic hepatitis C is ribavirin, which may have some activity. Many of the agents studied in chronic hepatitis B should also be investigated for the treatment of patients with chronic hepatitis C.