This case report describes a 32-year-old woman treated with indinavir who developed mild to moderate flank pain, malaise, and low-grade fever. Sterile pyuria preceded increased serum creatinine levels. Workup revealed persistent pyuria, normal-sized kidneys, a normal intravenous pyelography, and negative urinary cultures. Renal biopsy showed interstitial nephritis and chronic inflammation. Collecting ducts contained crystals. Two months after treatment with indinavir was discontinued, serum creatinine levels returned to normal and pyuria disappeared. Sterile pyuria in patients taking indinavir may help to identify patients at risk for renal dysfunction and interstitial nephritis. Markedly increasing the fluid intake above the recommended dosage may ameliorate or even reverse the process of tubulointerstitial disease.