A 51-year-old woman developed an acute onset of renal dysfunction accompanied by rash, lumbar pain, arthralgias, fever, eosinophiluria, and an elevated serum creatinine after 6 days of intravenous piperacillin-tazobactam therapy. On discontinuing piperacillin-tazobactam and after a 21-day course of prednisone, the patient's constitutional symptoms dissipated and her renal function returned to baseline. Acute interstitial nephritis has been reported as an adverse effect of many drugs, including antibiotics, but not, to our knowledge, after piperacillin-tazobactam. The time course of events suggested that piperacillin-tazobactam was the cause of acute interstitial nephritis in this patient.