The interpretation of small numbers of lymphoblasts or of nonspecific pleocytosis in the cerebrospinal fluid (CSF) of children with lymphoid malignancies is difficult. In this prospective study of 204 patients, 15 had white cell chamber counts of ≤10 cells/μl, with one or more blasts on a cytocentrifuged smear. Only 3/15 subsequently developed meningeal leukemia, and 4/15 remain in continuous complete remission. Among 53 patients with a chamber count >10 WBC/μl and no blasts, pleocytosis was associated with central nervous system (CNS) prophylaxis in half. Less common were viral syndromes, immune recovery, subsequent meningeal leukemia, active hematologic leukemia, the somnolence syndrome, leu-koencephalopathy, or reaction to a previous traumatic lumbar puncture.