: The original hepatitis C virus antibody test against the C100 antigen has been replaced by a second-generation recombinant immunoblot assay that detects antibodies against four viral antigens, one of which, against the nucleocapsid of the virus, is useful for earlier diagnosis of the acute stage. Polymerase chain reaction analysis of serum hepatitis C virus RNA remains the standard for diagnosing and following the course of the disease. It may be useful in identifying anti-hepatitis C virus patients who have underlying liver disease. Mutations in the viral envelope lead to different clinical types whose significance is still uncertain. The mode of infection in hepatitis C virus-positive patients who are neither drug abusers nor have a history of blood transfusion remains uncertain. Body secretions do not seem to contain the virus. Needle-sticks from a patient testing positive for hepatitis C virus RNA carry a 10% risk of transmitting the disease. Hepatitis C virus is being increasingly recognized as a cause of what was previously termed cryptogenic chronic liver disease. Hepatic histology shows a characteristic but not diagnostic picture, with lymphoid follicles prominent. An association of hepatitis C virus with essential mixed cryoglobulinemia has been found. Antibodies to type 1 liver and kidney microsomes are characteristic of type 11 autoimmune hepatitis and may be found in some patients testing positive for hepatitis C virus RNA, owing to cross-recognition of viral and type 11 autoimmune hepatitis antigens. There is a strong association between hepatitis C virus and hepatocellular carcinoma. Selection of patients and the regimes for antiviral treatment remain uncertain. The overall complete response rate without relapse is 25%. Hepatic transplantation is followed by reinfection of the graft with hepatitis C virus; the consequences are variable.