l-Asparaginase was administered intravenously by two dosage schedules to 19 children with acute leukemia refractory to conventional antileukemic agents. Nine patients with acute lymphocytic leukemia received the enzyme in a daily dosage of 4,000 I.U. per square meter of body surface area for 6 to 21 days. Ten patients, 7 with acute lymphocytic leukemia and 3 with acute myelocytic leukemia, received the enzyme in a dosage of 20,000 I.U. per square meter once weekly. Four patients with acute lymphocytic leukemia developed complete remission marrows. Two patients, one with acute lymphocytic leukemia and one with acute myelocytic leukemia, achieved partial remissions. Six patients died during the treatment period. All patients developed evidence of hepatic dysfunction. Toxicity appeared to be greater when l-asparaginase was administered daily rather than weekly. Prolongation of l-asparaginase therapy beyond 2 weeks is not indicated because of promptness of response by sensitive cells and potential toxicity of the agent.