Six regimens utilizing L-asparaginase in doses of 6,000 IU/M2, 2,000 IU/M2, and 500 IU/M2 in two separate schedules (consecutive and intermittent) along with vincristine and prednisone yielded remarkably similar response rates, approximating 70%, in 306 previously treated children with acute leukemia in relapse. The addition of daunorubicin to one regimen did not alter the response rate. Hypersensitivity reactions occurred in 5% and hyperglycemia in 7%. Lower doses of L-asparaginase significantly reduced the hypersensitivity rate but no such pattern was noted for hyperglycemia. A history of prior resistance to prednisone and vincristine significantly reduced the response rate.