Long-term neuropsychological complications such as attention and concentration disturbances, poor school performance, hyperexcitability, and even leukoencephalopathy have been described in children after chemotherapy for acute lymphoblastic leukemia. Elevation of the cerebrospinal fluid level of tau protein, associated with neuronal axons, is a neurodegenerative marker. The aim of the study was to assess the level of cerebrospinal fluid tau protein in children with acute lymphoblastic leukemia. The study included 26 patients with acute lymphoblastic leukemia and 19 patients with clinical symptoms of cerebrospinal meningitis (reference group). Tau protein levels were determined by enzyme-linked immunosorbent assay. Cerebrospinal fluid total protein level was not elevated in any of the samples. The examination was performed at diagnosis, after induction treatment, during consolidation, and after reinduction, i.e. before maintenance therapy. Neither age nor sex had an effect on tau protein levels in both groups. The mean tau protein value at diagnosis was 244.84 +/- 98.96 pg/mL in the study group (norm 300 pg/mL) and produced no correlation with initial leukocytosis, lactate dehydrogenase activity, or organomegaly at this point. Dynamic analysis revealed a statistically significant increase in tau protein after induction treatment (431.25 +/- 232.50) as compared with its level at diagnosis (244.84 +/- 98.96, P < 0.008) and later during treatment. The levels of tau protein at various points of treatment did not differ statistically significantly between the groups, except for the values obtained after termination of remission induction. The observed metabolic changes in tau protein, which is a known marker of neuronal damage, indicate that some patients are at a greater risk of central nervous system disorders. This finding requires further studies, also in reference to other central nervous system proteins, and confirms the necessity of long-term follow-up of leukemia patients.