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Beta-2-microglobulin determinations in cerebrospinal fluid (CSF) of patients with leukemia, lymphoma, and oat cell carcinoma were performed to evaluate the utility of this test in early detection of metastasis to the central nervous system (CNS). In the presence of CNS disease, significantly higher levels (P less than 0.001) were found than in normals or patients without CNS disease. Serial measurements were performed on two patients, and in all cases beta-2-microglobulin became elevated coincident with CNS relapse, and returned to normal as remission was achieved. Serial testing of CSF beta-2-microglobulin, in patients with cancers known to invade the CNS, should facilitate prompt treatment of CNS metastasis.