Tumor lysis syndrome (TLS) and renal failure remain significant causes of morbidity and mortality in children with newly diagnosed Burkitt's lymphoma and high white blood cell count acute lymphocytic leukemia (ALL) despite conventional management with aggressive hydration, alkalinization, allopurinol, and the slow introduction of chemotherapy. A subgroup of patients at very high risk for TLS and renal failure can be identified based on the level of serum lactate dehydrogenase (LDH) and urine output. We evaluated the prospective use of continuous veno-venous hemofiltration (CVVH), in addition to conventional management to prevent renal failure from tumor lysis, in three children with advanced abdominal Burkitt's lymphoma and in two children with high white blood cell count T-cell ALL who were at very high risk based on LDH and urine output. In this cohort of very high-risk patients, the LDH ratio (value at diagnosis/upper limit of normal) ranged from 0.88 to 10.3 and urine output from 0.13 to 4.7 ml/kg per hour. CVVH was begun at a mean time of 10.5 h before chemotherapy was initiated. Full-dose induction chemotherapy was begun within 24 h of diagnosis. After beginning CVVH, the uric acid levels decreased 46% prior to beginning chemotherapy and decreased to a mean of 4.2 mg/dl 24 h after chemotherapy was initiated. Four of the five patients had either no change or a drop in the serum creatinine. In patient one, blood urea nitrogen peaked at 58 mg/dl, and the creatinine at 4.7 mg/dl 6 days after beginning chemotherapy with a subsequent return to normal. Asymptomatic hypokalemia developed in all patients. After beginning chemotherapy, CVVH was continued for a mean of 85 h (range 70-91 h). No patient had complications secondary to CVVH. In summary, CVVH prevented renal failure secondary to TLS in 80% of these very high-risk patients. In the fifth patient, CVVH allowed full-dose chemotherapy to continue. The prospective use of CVVH could potentially decrease the morbidity and mortality associated with induction chemotherapy in very high-risk patients with a large tumor burden.