Acute tumor lysis syndrome after intrathecal methotrexate administration. A 44-year-old man had acute tumor lysis syndrome after a single dose of intrathecal methotrexate was administered for lymphomatous meningitis (high-grade, small noncleaved B-cell) in the setting of untreated systemic disease. The metabolic derangements reversed completely with conservative therapy and did not recur with subsequent treatment. Intrathecal methotrexate administration results in potentially toxic systemic methotrexate levels which persist longer than an equivalent systemic dose. Active central nervous system lymphoma may increase the duration of toxic levels in the circulation and contribute to the peripheral effects of the drug. The pathogenesis of tumor lysis syndrome in this patient and the mechanisms of systemic toxicity of intrathecal methotrexate are discussed. 