The incidence of recurrence of hepatitis B virus (HBV) following orthotopic liver transplantation (OLT) is as high as 80% when no attempt at prevention has been considered. HBV reinfection is associated with the reappearance of hepatitis B surface antigen (HBsAg) and HBV DNA in serum and, in most cases, with rapid severe graft damage. Immunoprophylaxis using polyclonal anti-HBs immunoglobulins reduces the risk of recurrence but this long-term therapy remains highly expensive. In this report, we use fresh frozen plasma (FFP) with high titers of anti-HBs immunoglobulins in an attempt to reduce HBV recurrence. From July 1987 to September 1993, 11 patients underwent OLT for HBV-related liver disease (18% of our OLT patients). FFP were administered to 6 patients continually for 7 to 46 months. Only one patient, under long-term immunosuppressive treatment before OLT, was reinfected 7 months after OLT. Rapid development of graft failure was observed with histologic manifestations of a fibrosing cholestatic hepatitis, leading to patient death after 12.5 months with concomitant bacterial infection. In this protocol, the rate of reappearance of HBsAg was 17%, a figure which can be favorably compared with other reports. All patients were subsequently tested for HCV and HIV and remained negative. In conclusion, FFP with high titers of anti-HBs immunoglobulins is at least as effective as polyclonal anti-HBs immunoglobulins in reducing the rate of HBV recurrence following OLT. The estimated cost of this new immunoprophylaxis method is less than 10% of the classical prophylaxis based on purified human polyclonal anti-HBs immunoglobulins.