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The influence of central nervous system (CNS)-directed chemotherapy on intelligence remains controversial. In this study, we investigated the influence of treatment on intellectual development in acute lymphoblastic leukemia (ALL) and brain tumor patients undergoing CNS-directed treatments.Among patients treated in the Department of Pediatrics, St Luke's International Hospital between April 2000 and March 2009, the subjects were 38 patients with ALL or brain tumors who underwent regular Wechsler intelligence tests.The subjects consisted of 26 patients with ALL and 12 with brain tumors. Prophylactic cranial irradiation was not performed in patients with ALL, whereas it was done for all those with brain tumor. In patients with ALL, the IQ 1 year later was not changed from the start of treatment. In those with brain tumors, the verbal IQ 1 year later was significantly lower than that at the start of treatment. In patients with ALL, intelligence tests were performed 3 years after the start of treatment and there were no marked changes between the two time-points (n= 11). In those with a brain tumor, intellectual functions further decreased after the completion of treatment to as late as 5 years after the initiation of treatment (n= 7).There is no intellectual impairment in any patient with ALL at post-treatment follow-up 3 years after the start of treatment, while intelligence is serially reduced in brain tumor patients. An innovative intervention may be needed for this group of patients.