Non-A, non-B hepatitis is the most common serious complication of blood transfusion and also occurs in a sporadic form whose routes of transmission are currently unknown. While generally mild in its acute presentation, non-A, non-B hepatitis frequently progresses to chronic hepatitis which may eventuate in cirrhosis and hepatocellular carcinoma. The disease is caused by a small, enveloped RNA virus now designated hepatitis C virus, which has similarities to the flaviviruses. Studies using the recently developed antibody assay have indicated that hepatitis C virus is the predominant agent of both transfusion-associated and sporadic non-A, non-B hepatitis. In 50-85% of transfusion-associated cases, a donor can be found who is positive for antibodies to the hepatitis C virus. Current data indicate that these antibodies are present in approx. 0.5% of blood donors in the United States and Europe, 1.5% in Japan and 6% in Africa, as well as in 60-80% of haemophiliacs and intravenous drug abusers and approx. 20% of dialysis patients. With changes in donor selection and transfusion practices, the incidence of transfusion-associated non-A, non-B hepatitis has declined from rates of 5-10% prior to 1985 to estimated current rates of 2-4%. The introduction of the anti-HCV test should effect an additional 50% reduction in transfusion-associated non-A, non-B hepatitis. In addition to these preventive measures, effective therapy now appears at hand in the form of alpha-interferon. The efficacy of other antiviral agents and the potential for combination therapies also need to be explored.