The Children's Cancer Study Group has organised two therapeutic clinical trials designed to evaluate the efficacy of various types and doses of CNS prophylaxis in the treatment of childhood acute lymphoblastic leukaemia. Of 478 previously untreated patients who subsequently achieved an initial marrow remission, 299 were randomised to receive 2400 rad craniospinal radiation therapy (RT) or 2400 rad cranial RT plus intrathecal methotrexate (i.t. MTX) while the remaining 179 patients were randomised between the same two regimens using a radiation dose of 1800 rad. All patients received identical induction and maintenance chemotherapy. Comparison of the two studies indicated that reduction of the dose of CNS radiation from 2400 rad to 1800 rad did not result in a significant increase in the frequency of CNS relapse, bone marrow relapse, or death. Moreover, no significant differences were observed when analyses were done within prognostic risk groups. Randomised trials with RT doses lower than 1800 rad or with i.t. chemotherapy alone should be considered to determine the most effective and least toxic forms of CNS prophylaxis.