Abstract Epstein-Barr virus (EBV) infection is a benign disease, which may occasionally be fatal, particularly in children and immunocompromised patients. Epstein-Barr virus infection is rare in elderly subjects and seems to have a self-limited course. A case of fatal liver failure due to chronic active EBV infection in a 75-year-old man is described. The etiology was established postmortem by cellular expression of EBV-DNA in liver and lymphatic tissue. This patient meets the diagnostic criteria of a case definition for a highly probable “severe chronic active EBV syndrome.” Either suspected or unsuspected, the long-term prognosis of this syndrome is poor and its mortality high.