RATIONALE AND OBJECTIVES: The authors evaluate quantitatively brain atrophy induced by central nervous system prophylaxis in children treated for acute lymphoblastic leukemia during and after therapy completion. METHODS: Measurements of the width of the subarachnoid compartments were performed in 243 brain computed tomography (CT) examinations of 196 children examined during (125) and/or after (71) treatment for acute lymphoblastic leukemia without central nervous system involvement. Data were compared with normative data. RESULTS: Diffuse brain atrophy was observed in 74% and 65% of the CT examinations performed during and after cessation of treatment, respectively. The highest incidence of brain atrophy (78%) occurred during the administration of intrathecal chemotherapy. All children younger than 2 years of age exhibited brain atrophy. CONCLUSIONS: Brain atrophy is the principal CT finding in the majority of children treated for acute lymphoblastic leukemia and it can be attributed mainly to intrathecal chemotherapy. This finding can be observed long after therapy completion.