Four patients with acute lymphocytic leukemia previously treated with conventional chemotherapy received intramuscular L-asparaginase in combination with other chemotherapy for reinduction and maintenance therapy. These patients received the L-asparaginase for 8, 14, 27, and 34+ months without demonstrating any significant adverse effects. Only 1 of the 4 was clearly resistant to the other chemo-therapy, and 3 of 4 had recurrence of their disease while receiving L-asparaginase. L-asparaginase can be added to reinduction and maintenance regimens of patients resistant to other chemotherapy and is well tolerated for long periods when given intramuscularly weekly with other immunosuppressant agents.