Hepatitis C virus (HCV) is the leading cause of blood-borne and community acquired non-A, non-B hepatitis. HCV infection has been estimated to affect about 3 per cent of the population worldwide. Higher prevalence occurs in high-risk groups, which include patients with a history of intravenous drug abuse and those multiply transfused before the introduction of mass screening of donated blood for viral antibodies. The virus persists in approximately 80 per cent of those infected. Twenty per cent of patients with chronic infection progress to cirrhosis after an average of 20 years. Hepatocellular carcinoma is a significant risk in these, occurring in around 3 per cent annually. Virus antigen has been demonstrated in the cytoplasm of hepatocytes of infected patients by immunohistochemistry although the sensitivity of detection of antigen has varied from study to study. In previous studies, frozen tissue fixed in acetone/chloroform has given the most reliable results. Epitopes on the core and NS4 proteins of the virus are preserved following formaldehyde fixation and wax embedding of tissues, but monoclonal antibodies to these epitopes have shown unacceptable cross-reactions with host antigens. This antibody is a new monoclonal antibody raised against a recombinant NS3 protein. It recognises an epitope stable to routine processing and exhibits minimal cross-reactivity with normal or diseased liver. Using a five-step peroxidase, anti-peroxidase detection system, virus-specific staining has been demonstrated with this antibody in the cytoplasm of hepatocytes in acute HCV infection and in immunosuppressed patients with chronic HCV infection. The immunohistochemical detection of antigen in the liver of immunocompetent patients with established chronic HCV infection is currently being evaluated.