We retrospectively reviewed our experience of Epstein-Barr virus (EBV)-associated acute renal failure. Of 165 previously healthy children hospitalized with serologically proven primary EBV infection, 8 had acute renal failure, of whom 5 (group A) did not have virus-associated hemophagocytic syndrome (VAHS), while 3 (group B) did have VAHS. All had complications in four or more organ systems. Two patients in group A had renal biopsies showing acute tubulointerstitial nephritis, and the clinical and laboratory findings in the other 3 group A patients were consistent with acute tubulointerstitial nephritis. Acyclovir was used in 1 patient, but she died of hepatic failure and pulmonary hemorrhage. The other 4 spontaneously recovered renal function after supportive care, including hemodialysis in 1 patient. Our experience does not support the routine use of corticosteroids or antiviral agents in these patients. Children in group B had a relatively normal urinalysis. Renal biopsies were not performed, but their presentations were compatible with acute tubular necrosis. We conclude that EBV should be considered as a possible etiological agent in all children presenting with acute renal failure of unknown cause. The diagnosis depends on a high index of suspicion and careful serological evaluation in atypical cases.