Among 108 children under 20 years of age with acute lymphocytic leukemia, vincristine sulfate and prednisone induced complete remissions in 96% (43) of the patients with newly diagnosed disease and in 83% (52) of the previously treated patients. Methotrexate administered orally or intramuscularly twice a week maintained the remissions similarly. The median duration of remission for 42 newly treated patients was 10.4 months (orally) versus 8.9 months (intramuscularly), and for 51 previously treated patients it was 5.1 months (orally) and 4.9 months (intramuscularly). The duration of methotrexate-maintained remission was shorter for subsequent remissions especially if a previous remission had been maintained with methotrexate. Possibility of a new type of toxic reaction occurring during methotrexate maintenance is suggested by the high frequency of pneumonitis (38 of 93 children). Other toxic manifestations were controlled by diminished dosages of methotrexate.