We describe a patient with hepatitis B antigenemia, who received a simultaneous pancreas and kidney transplant, developed reactivation of hepatitis B virus infection with aminotransferase elevation, and unexpectedly suffered an acute rejection episode within a few weeks after initiation of lamivudine therapy. At the time of rejection diagnosis, the cyclosporin A (CyA) trough level was 2 times lower than before the start of lamivudine therapy. Only an improvement in liver CyA metabolism in the course of lamivudine therapy can explain such an essential decline. Thus, it is important to emphasize how crucial it is to frequently monitor the CyA level in the early period of lamivudine therapy in transplanted patients with hepatitis to ensure adequate immunosuppression and to avoid acute rejection episodes.