The authors have successfully used combination ganciclovir and foscarnet chemotherapy to control viral replication following liver transplantation in a patient with severe recurrence of hepatitis B virus (HBV) infection. The disease was characterized by extremely high viraemias, deteriorating liver function, and high levels of intra-hepatic hepatitis B core antigen (HBcAg) and hepatitis B surface antigen (HBsAg). Treatment resulted in a greater than 30-fold reduction in serum HBV DNA and HBsAg levels. Liver function tests returned to normal and the histological progression of the disease was arrested. Hepatic cytoplasmic HBsAg decreased substantially but there was little change in HBcAg, implicating HBsAg rather than HBcAg in the liver injury. Combination antiviral chemotherapy using agents such as ganciclovir and foscarnet may offer a new approach to the management of post-transplant recurrence of HBV.