Asparaginase was administered to children with acute lymphocytic leukemia in dosages less than those generally used. The objectives were to determine whether toxicity of the enzyme could be reduced without loss of efficacy, and to compare weekly with twice weekly administration. In five of 11 children who received 5,000 international units (IU)/sq m twice weekly for four doses and four of ten who received 10,000 IU/sq m once weekly for two doses, examination of bone marrow showed complete remission. Although the usual asparaginase-induced toxic reactions occurred, there were no deaths due to toxic reaction and no clinical signs of pancreatic dysfunction. Toxic reactions were comparable in the once weekly and twice weekly groups. Toxicity can be decreased without loss of efficacy by using these reduced dosage schedules.