Hepatitis C virus (HCV) is important to the liver transplant recipient for several reasons. First, chronic HCV infection is a frequent cause of end-stage liver disease in North America and Europe, where the majority of liver transplants are performed. Second, recurrence of HCV after liver transplantation is almost universal so that many liver transplant recipients with and without overt hepatitis are viraemic. Third, HCV infection in the organ donor and/or in the blood transfused in the peri-transplant period make acquisition of HCV possible. Finally, liver transplantation for chronic HCV infection represents a major financial burden to the health-care system in the USA and worldwide. Histological hepatitis not due to HBV or cytomegalovirus (CMV) is present in 14-35% of allografts from patients undergoing liver transplantation, and the majority of this is due to HCV infection. HCV infection recurs post-transplant in almost all patients with pre-transplant infection. Proof that HCV does recur has been provided by the sequencing of the hypervariable domain of the E2/NS1 region. The magnitude of HCV infection is underestimated by using serological assays in this immunosuppressed population. Using the b-DNA assay, HCV-RNA levels have been shown to increase in patients with recurrent infection. The long-term consequences remain to be defined but post-transplantation HCV infection is generally much less devastating than post-transplantation HBV infection, and many patients have clinically silent disease. It is likely that a carrier state exists in immunosuppressed transplant recipients since high HCV-RNA levels occur in the absence of liver damage. In one study, 1, 2 and 3 year patient survival rates were shown to be comparable in patients with chronic active HCV infection and with cryptogenic cirrhosis (94, 89 and 87%, and 84, 84 and 73%, respectively). A more recent study from the University of Pittsburgh which compared the outcome of a larger number of HCV-infected patients (n = 237) with a large number of control patients with non-viral disease (n = 801), showed that indeed HCV infection does impact negatively on both patient and graft survival (1, 2 and 3 year patient survival in the study and control groups of 78, 68 and 66% and 84, 82 and 78%, respectively, P = 0.001). Undoubtedly with time, the full impact of recurrent HCV infection will become apparent, although short-term survival is sufficiently good to warrant continued transplantation of this group of patients.(ABSTRACT TRUNCATED AT 400 WORDS)