The aims were twofold. Firstly, to assess the clinical significance of staging investigations; in particular the significance of molecular virological investigations in terms of disease diagnosis and prognosis. The role of non-invasive investigations in staging the disease process was also considered. Secondly, the impact of chronic hepatitis C infection was assessed in two populations; patients diagnosed as having hepatocellular carcinoma and those immunocompromised chronic HIV infection. In the Scottish population studied, both serum and intrahepatic virus levels were not determined by host factors (age of patient, mode or duration of infection) or by virus factors (HCV genotype). Likewise, there was no correlation between serum and liver HCV RNA levels demonstrated; however, those data did demonstrate that repetitive negative RT-PCR for HCV RNA in serum did not indicate absence of HCV from the liver. Pilot studies of the two non-invasive investigations in this population showed both to be reliable in predicting the presence of hepatic cirrhosis in patients infected with HCV. Amongst the intravenous drug abusers with chronic HIV infection, HCV did not influence either the clinical progression of HIV disease to AIDS and it was not associated with a more rapid immunological decline. Chronic HCV infection was identified as a major risk factor for the development of hepatocellular carcinoma. Molecular virological staging investigations should be interpreted with caution in chronic HCV infection; their most significant role is likely to be the initiation and monitoring of therapy rather than the inference of disease prognosis. Non-invasive investigations of hepatic cirrhosis are likely to be useful tests when a liver biopsy is contraindicated, although they should be first validated in larger, well described populations.