Enolase isoenzymes were measured in the cerebrospinal fluid of seven consecutive children with lymphoblastic leukemia who developed meningeal (CNS) leukemia. Assays were performed at the time CNS disease was discovered and during the subsequent 4 weeks. Three of the seven were also examined 1-3 months before CNS relapse was confirmed. Fourteen children on similar systemic therapy without CNS infiltration served as controls. Prior to and at the onset of CNS disease alpha enolase was elevated in all patients studied. The gamma form was raised in only one beforehand and only three at the time of relapse. The alpha isoenzyme was related to the blast cell count and fell during therapy in all but one child, whereas the gamma was not and showed no significant change. The three patients with raised gamma enolase were the only children with other than common lymphoblastic leukemia. There was no clear indication whether either enzyme concentration had any importance in terms of disease outcome, although one child developed a further CNS relapse 10 months later. He was the only patient whose alpha enolase rose following intrathecal methotrexate. Neuronal disruption due to common lymphoblastic leukemia in the CNS appears to be minimal. Other types of leukemia may give rise to more neuronal damage. The alpha isoenzyme, from glial tissue and malignant cells, may be elevated even in the absence of detectable blasts in the cerebrospinal fluid and may be a sensitive marker of CNS infiltration in such circumstances.