BACKGROUND Neurological complications and EEG slowing frequently occur in children undergoing induction treatment for acute lymphoblastic leukemia (ALL). Disease-related factors and treatment-related toxicity are believed to play causative roles. We wanted to elucidate the etiology further by serial EEG examinations and parallel CSF amino acid analyses. METHODS Twenty-nine children participated in the study. EEG examinations with quantitative computerized analysis were scheduled on day 1, 10, 29, and 59 of protocol I of BFM-ALL 90 and 95 Study Protocols. CSF analysis for amino acids was carried out on day 1, 15, 29, 45, and 59. RESULTS A total of 21 of 25 available EEGs showed slight-to-moderate slowing already at diagnosis. The abundance of slow waves was significantly correlated to the white blood count and the CSF glutamine concentration. The EEGs significantly worsened during the first 10 days of treatment with prednisone, VCR, daunorubicin, and intrathecal methotrexate. The following treatment including asparaginase (ASP) gave rise to depletion of CSF from asparagine and a rise of aspartate; glutamine, and glutamate did not follow this pattern. The EEGs remained abnormal, but did not worsen further; the CSF amino acid changes were not related to the EEG. During the subsequent consolidation treatment, the EEGs normalized despite administration of cyclophosphamide, cytara bine, intrathecal methotrexate, and mercaptopurin. CONCLUSIONS The greater part of EEG changes observed in the early treatment of ALL is due to disease-related factors. Treatment with prednisone, vincristine, and to a much lesser degree asparaginase aggravates the pre-existing encephalopathy. Depletion of CSF from asparagine does not give rise to additional changes. In the second month, the EEG normalizes despite ongoing treatment with different cytotoxic drugs.