Hepatitis B virus (HBV) reactivation, a well-known complication in immunosuppressed patients, can give rise to acute hepatitis and even fatal fulminant hepatitis. Three Japanese males with non-Hodgkin's lymphoma (NHL) who were carriers of HBV received high-dose chemotherapy followed by autologous peripheral blood stem cell transplantation (PBSCT). To prevent HBV reactivation, all received oral lamivudine (150 mg/day), a nucleoside analogue, at the start of chemotherapy. All were treated at full-dose intensity, including corticosteroids, without modification of treatment regimens. All three patients completed the total course of chemotherapy and PBSCT, with no signs of HBV reactivation. Peripheral blood stem cell (PBSC) harvests and hematological recoveries after transplantation were not affected by lamivudine, which was continued for at least 16 weeks after transplantation. HBV-DNA and DNA polymerase levels remained negative/normal after discontinuation of lamivudine. Lamivudine effectively inhibits HBV replication and has few serious adverse effects, particularly those related to hematopoiesis. Thus, prophylactic use of lamivudine from initiation of chemotherapy deserves consideration in the treatment of HBV carriers who require immunosuppressive chemotherapy, and may prevent HBV reactivation.