To detect early relapse in the central nervous systems (CNS) of patients with acute leukemia or lymphoma, we measured levels of beta 2-microglobulin (beta 2 m) in serum and cerebrospinal fluid (CSF). CSF levels were significantly higher in patients with leukemia (P < 0.001) or lymphoma (P < 0.02) with clinical evidence of CNS involvement than in those without this complication. When serum and CSF levels were measured simultaneously, the CSF level of beta 2 m was significantly higher than the serum level in patients with acute leukemia and lymphoma with CNS involvement (P = 0.05), but not in patients without CNS involvement. Serial determination of CSF beta 2 m correlated well with the clinical appearance and disappearance of CNS involvement. These data suggest that serial and simultaneous determination of beta 2 m in serum and CSF may be useful in early diagnosis of CNS involvement and in monitoring intrathecal therapy in patients with acute leukemia or lymphoma.