Beta 2-microglobulin levels were determined in the cerebrospinal fluid (CSF) of 119 children (ages 1 1/2 to 18 years) with malignant conditions; 87 with acute lymphoblastic leukemia, 9 with acute myeloblastic leukemia, 15 with lymphoma, and 8 with solid tumours. A total of 491 CSF specimens and 202 serum specimens were analyzed over a 12-month period. The mean CSF β 2-Microglobulin and serum β 2-microglobulin were 1.11 ± 0.58 mg/L and 1.5 ± 0.64 mg/L respectively and were not different from the mean CSF (1.20 ± 0.45 mg/L) and serum β 2-Microglobulin levels (1.70 ± 0.45 mg/L) found in control patients. Meningeal leukemia was diagnosed on the basis of cytology in 7 patients. No elevation of CSF β 2-microglobulin was found in any specimen at the time of CNS disease. Eleven other patients showed a transient rise in CSF β 2-microglobulin above the reference range (>2.1 mg/L). No evidence of CNS involvement was found in any of these patients. Five of these patients had received a combination of intrathecal methotrexate and irradiation therapy within the previous 4 months. A transient rise in CSF β 2-Microglobulin (2–3-fold increase over baseline CSF levels), which did not exceed the upper limit of the reference range was seen in 5 of 7 other children receiving the above therapy. Our study fails to demonstrate the usefulness of CSF β 2-Microglobulin for the diagnosis of CNS metastases but suggests that a transient elevation of CSF β 2-microglobulin may occur after intrathecal methotrexate and irradiation therapy.