An elevated serum soluble interleukin-2 receptor (SIL-2R) has been noted in various hematological malignancies and conditions associated with active T-cell responses. Its appearance has also correlated with disease activity and tumor burden. Since few studies have been reported concerning SIL-2R in cerebrospinal fluid (CSF), work was undertaken to try to find if SIL-2R could be detected in the CSF of patients with acute lymphocytic leukemia (ALL) or non-Hodgkin's lymphoma (NHL), and whether it could become a clinical predictor of the central nervous system (CNS) involvement, and its response to therapy. Preliminary results showed that 1) the CSF SIL-2R is usually detectable in very low level with a mean of 15.1 +/- 14.2 units/ml compared with the mean serum level of 338.3 +/- 135.5 units/ml in eight normal controls; 2) there was no significant difference in the mean serum and CSF SIL-2R in five patients with ALL in a complete remission state compared with normal controls, while two ALL patients with CNS relapse and two NHL patients with CNS involvement had high levels of SIL-2R in CSF. High serum and low CSF SIL-2R levels were noted in another ALL case suffering from bone marrow relapse but without CNS relapse. It was also noted that decreased CSF SIL-2R concentration occurred subsequent to intrathecal chemotherapy in two ALL patients. From these results, we conclude that CSF SIL-2R might become a useful indicator of CNS involvement in patients with hematological malignancies and may predict response to chemotherapy.