Infectious mononucleosis, most commonly caused by Epstein-Barr virus (EBV), is generally a benign, self-limited illness. Occasionally, however, more severe complications may arise such as acute renal insufficiency. While subclinical renal involvement appears to be relatively common in patients with infectious mononucleosis, patients with significant renal parenchymal dysfunction have rarely been described in the English-language literature. In this report, we review 27 previous cases and present a case of oliguric renal failure complicating heterophil-positive infectious mononucleosis. The patient required hemodialysis but recovered promptly with treatment with the combination of corticosteroids plus acyclovir. Renal biopsy revealed interstitial nephritis, and immunoperoxidase studies demonstrated a predominance of suppressor/cytotoxic T cells, which has been described in only one previous case report. In situ hybridization done on renal biopsy tissue failed to reveal evidence of EBV-encoded RNA-l. Acute renal failure in infectious mononucleosis is rare, often self-limited, and usually caused by interstitial nephritis that is likely the result ofimmunopathologic injury precipitated by EBV infection.