At the present time, a successful regimen for the eradication of occult meningeal leukemia, following induction of a first complete remission in acute lymphoid and undifferentiated childhood leukemia, is the combination of cranial radiotherapy in a dose of 1800 rads in 10 fractions in 12–14 days with six doses of intrathecal methotrexate. This regimen, when given with prednisone and vincristine with or without L-asparaginase for induction and daily oral 6-mercapto-purine and weekly methotrexate for maintenance, can be expected to give a relapse rate for isolated meningeal leukemia of approximately 5% during the first 2 years of follow-up. A modification of this regimen utilizing craniospinal radiation with prior and concurrent intrathecal methotrexate is given for the treatment of overt meningeal leukemia at diagnosis or for an isolated first relapse with meningeal leukemia. Radiation technique and morbidity are discussed.