The authors report the case of a 47-year-old woman in whom a systemic illness developed characterized by fever, malaise, abnormal liver function results, and acute renal failure after treatment for presumed urinary tract infection with levofloxacin. Because of suspicion of an allergic drug reaction, all medications were discontinued, but the patient remained febrile with renal failure for 18 days. Complete workup for presumed vasculitis, autoimmune illness, or infectious etiologies was negative, and the patient underwent both renal and liver biopsy. Liver biopsy results showed nonspecific changes. Renal biopsy disclosed extensive granulomatous interstitial nephritis with associated granulomatous vasculitis. The patient was begun on oral steroids with rapid defervescence of fever and progressive normalization of renal function. The authors discuss the association of granulomatous nephritis with drugs and review the known nephrotoxicity of fluoroquinolones.