Unexpected nephrotoxicity has been described in high-dose, bolus ifosfamide (IFF) therapy. Renal injury is not thought to occur in patients receiving fractionated schedules, although microscopic hematuria from bladder irritation is not uncommon. IFF is undergoing trials in patients with malignant lymphomas, gynecologic malignancies, and advanced sarcomas and has shown promising results. This report describes renal abnormalities in four patients with malignant lymphoma receiving single-agent, fractionated IFF and suggests a proximal tubular defect in two patients who were studied in greater detail. These findings suggest an unreported and unique toxicity of IFF when given in smaller, fractionated doses.