After remission-induction chemotherapy in 31 patients with acute lymphoblastic leukaemia, patients immediately received CNS prophylaxis. Thirteen patients received triple intrathecal drug therapy, while 18 patients received intrathecal methotrexate and cranial irradiation; systematic chemotherapy was administered as well to both groups. Six patients developed CNS leukaemia during complete remission, 2 in the non-radiated patients and 4 in patients who had received cranial irradiation. Drug chemoprophylaxis may therefore substitute cranial radiotherapy when effective systemic regimens are used. Such CNS chemoprophylaxis will result in fewer, long-term CNS side-effects.