The progress of immunosuppressive therapy has made heart transplantation the standard therapy for end-stage heart failure. However, humoral rejection of the cardiac allograft is still a challenging problem associated with high incidence of graft loss and patient mortality. The present patient developed profound cardiogenic shock requiring extracorporeal life support on the 8th day after heart transplantation. Endomyocardial biopsy revealed no cellular rejection, and complement component C4d was positively stained on the capillary endothelium. The patient was successfully treated with repeated plasmapheresis and administration of anti-CD20 monoclonal antibody, rituximab, as well as with steroid pulse and increased standard immunosuppressive medication.