Purpose: The purpose of this phase I study was to determine the toxicities and response to continuous infusion carboplatin in combination with a fixed dose of etoposide (VP-16) in children with refractory acute leukemia. Patients and Methods: From January 1989 to February 1992, 20 patients received 28 courses of treatment. Each course of treatment consisted of a 1- hour intravenous (IV) infusion of VP-16 100 mg/m2/d for 5 days, followed by a 23-hour IV infusion of carboplatin each day. The initial, total 5-day dose of carboplatin (1,000 mg/m2) was escalated by 250- to 375-mg increments to a final, total dose of 1,875 mg/m2 over 5 days. Results: Significant marrow suppression was observed in all patients, with prolonged marrow aplasia at the 1,875-mg/m2 dose level. Grade III diarrhea occurred in three patients; 10 patients experienced life-threatening infection and three had severe thrombocytopenic bleeding. Major marrow responses (two complete remissions and two partial remissions) occurred in four patients (20%). Conclusion: In view of the apparent antileukemic efficacy and minimal extramedullary toxicity, carboplatin deserves further study in a phase II trial.