The cerebrospinal fluid (CSF) of 22 consecutive untreated children with acute lymphocytic leukemia who entered total study VII from September to December 1971 at St. Jude Children’s Research Hospital was examined. Four patients had periodic acid-Schiff (PAS)-positive, Sudan black B- and peroxidase-negative lymphoblasts in the CSF at diagnosis. Two of the 4 developed meningeal leukemia 3 and 5 months following diagnosis. None revealed pleocytosis and/or detectable atypical cells on a Wright-stained smear of CSF sediment at diagnosis. Two patients had no more detectable PAS-positive lymphoblasts after ‘prophylactic’ central nervous system (CNS) radiotherapy. They are in continuous complete remission for 9 and 10 months. The recognition of a small number of CSF-abnormal cells with PAS reaction and the differentiation of blasts from inflammatory cells may allow an earlier diagnosis and treatment of CNS involvement in childhood acute lymphocytic leukemia.