Hepatitis C virus-induced liver disease is becoming a main indication for liver transplantation. Recurrence of hepatitis after transplantation has been reported, but its long-term consequences are unknown. Seventy-nine patients positive for hepatitis C virus (group 1) and 106 subjects negative for hepatitis C virus antibody (group 2) with a mean follow-up of 4 yr were retrospectively studied by means of serology, nested polymerase chain reaction and branched-DNA technology before and after liver transplantation. The actuarial rates of hepatitis C virus-related acute hepatitis were 72% and 20% at 4 yr in groups 1 and 2, respectively. Progression to chronic active hepatitis occurred in 61% and 36% of the subjects within 3 yr of the onset of recurrent and acquired hepatitis, respectively. No case of acute graft failure and two cases of cirrhosis were related to recurrent or acquired hepatitis C virus liver disease. Hepatitis C virus RNA levels were significantly increased in cases of hepatitis after transplantation. In contrast, the pretransplant hepatitis C virus RNA level was not predictive of recurrence. Our results establish the general persistence of hepatitis C virus infection after liver transplantation, the frequency and the severe course of recurrent liver disease. However, liver transplantation in hepatitis C virus antibody-positive patients still has a good medium-term prognosis.