AbstractThe cerebral spinal fluid (CSF)‐protein profiles of ten children with previously untreated acute lymphoblastic leukemia (ALL) were investigated by agarose gel electrophoresis. The profiles were determined at diagnosis and during the fifth to eighth week of treatment when preventive therapy for central nervous system (CNS) leukemia (skull) irradiation, intrathecal methotrexate (ithMTX) was administered. The profiles were compared with those obtained from a control group of 67 children and those from 42 patients with acute aseptic meningitis. The data from the latter group demonstrated the CSF‐protein pattern of partial blood‐CSF barrier (B‐CSF‐B) breakdown. The children with ALL showed no or only minor signs of a B‐CSF‐B impairment at diagnosis and after four weeks of systemic treatment. However, CSF changes indicative of a lesion of the B‐CSF‐B increased in all children continuously during CNS prophylaxis. The protein profile at the end of combined chemotherapy and radiotherapy was very similar to that in patients with acute aseptic meningitis. These observations point to neurotoxic side effects on the CNS barrier system with the combination of cranial radiation and ithMTX. A striking finding was restricted heterogeneity of γ‐globulin, observed in the CSF of nine out of the ten children with ALL before or during treatment. The significance of this ab