Cytosine arabinoside (ara-C) and uracil arabinoside (ara-U) levels were measured in the plasma, cerebrospinal fluid (CSF), and urine of 10 patients exhibiting primary central nervous system lymphoma who received 31 infusions of high-dose ara-C (3 g/m2) as part of their treatment regimen. Peak plasma and CSF ara-C levels were 10.8 and 1.5 micrograms/ml, respectively. Ara-C was cleared more rapidly from plasma than from CSF. Ara-U appeared rapidly in both plasma and CSF, reaching a peak that was 10 times higher than the corresponding ara-C concentration (104 and 11.2 micrograms/ml, respectively). Only 4%-6% of the dose was excreted unchanged in the urine, but 63%-73% of it appeared as ara-U within the first 24 h. The presence of leptomeningeal lymphoma did not affect the CSF level of ara-C or ara-U.