Allograft infection in hepatitis B surface antigen (HBsAg)-positive patients undergoing liver transplant (OLT) is still significant, despite post-transplant prophylaxis with high doses of immunoglobulin to HBsAg. Baseline status and post-OLT levels of viraemia and wild-type and hepatitis B e antigen (HBeAg)-negative hepatitis B virus (HBV) were correlated with the clinical course of 16 consecutive HBsAg carriers. positive for hepatitis B e antibody, with hepatocellular carcinoma who underwent OLT and received permanent post-OLT prophylaxis with antibody to HBsAg (HBsAb). Fourteen patients had less than 10(3) HBV genome equivalents ml(-1) (eq ml[-1]) at baseline and remained HBV free after a median of 36 months following OLT. Two patients with mean pre-OLT viraemia higher than 10(5) genome eq ml(-1) and prevalent HBeAg-negative HBV viraemia before OLT suffered a severe graft hepatitis. Interferon-alpha2b (3 MU m(-2) per day) was able to reduce viraemia in both patients and to revert the clinical course of the infection in one, who remained infection-free 22 months after IFN treatment. Fourteen patients had less than 10(3) HBV genome eq ml(-1) at baseline and remained HBV free, after a median of 36 months following OLT, with permanent HBsAb immunoprophylaxis. These observations suggest that the quantitative analysis of HBV pre-OLT viraemia levels may provide a very useful tool for predicting the ideal time of liver replacement. Clinical trials on the use of antiviral drugs capable of inhibiting HBV serum levels before liver transplantation should be pursued on this premise.