Epstein-Barr virus (EBV) infection is common in adolescence, but fulminant infection is very rare. A 40-year-old man presented with high fever and sore throat. Symptoms, including cervical lymphadenopathy, jaundice, atypical lymphocytosis, respiratory distress and oliguria, suggested infectious mononucleosis with multiple organ failure that required mechanical ventilation and renal replacement therapy. Virus markers were consistent with primary EBV infection. Renal function was gradually improved by corticosteroid therapy. Renal biopsy revealed acute tubulointerstitial nephritis. In situ hybridizaion EBV-encoded RNA 1 did not show the presence of virus in the kidney, but acute kidney injury may be explained by cytotoxic/suppressor T lymphocyte infiltration.