Transmission of hepatitis B infection has been reported in liver transplant recipients whose donor livers were negative for hepatitis B surface antigen (HBsAg) and positive for antibody to hepatitis B core antigen (anti-HBc). These infections usually have a mild clinical course and no adverse effects on survival. However, the outcome of liver transplant recipients with serologic evidence of past infection to hepatitis B virus (HBV) is unknown. The prevalence of HBV DNA positivity by polymerase chain reaction (PCR) pretransplantation in HBsAg-negative, anti-HBc-positive people is reported to be 0% to 32%. To assess the prevalence of HBV DNA in pretransplantation serum and liver tissue and to determine the clinical outcome of HBsAg-negative, anti-HBc-positive recipients, we retrospectively reviewed the first 693 orthotopic liver transplantations performed at Mayo Clinic between March 19, 1985, and May 25, 1996. Pretransplantation specimens of frozen serum and liver tissue were available for HBV DNA by PCR for 35 of 56 HBsAg-negative, anti-HBc-positive recipients. Twenty-two recipients had positive serologic findings for anti-HBc alone, and 13 were positive for anti-HBc and antibody to HBsAg (anti-HBs). Pretransplantation prevalence of HBV DNA in HBsAg-negative, anti-HBc-positive recipients was 6% (serum) to 29% (liver). Of those recipients whose liver was HBV DNA-positive pretransplantation, 40% also had evidence of HBV DNA in posttransplantation liver biopsy specimens, and this finding was more common in patients co-infected with hepatitis C. None of the recipients became antigenemic (HBsAg-positive) or developed clinical hepatitis B posttransplantation. Thus, prophylactic intervention (eg, antiviral or antinucleoside analog therapy) is not warranted after liver transplantation in HBsAg-negative, anti-HBc-positive recipients. In our experience, infected donor livers are the most common source of de novo posttransplantation hepatitis B infection in transplant recipients.