The occurrence of major neurologic disturbances is a rare complication of intrathecal cytotoxic drug administration. We describe the case of a 30-year old man with relapsed lymphoblastic lymphoma and CNS involvement who was treated by systemic chemotherapy (ESHAP) and intrathecal injections of methotrexate, cytarabine, thiotepa and hydrocortisone. Thereafter he developed persistent paraplegia with sensory and sphincteric insufficiency. The role of the drug in causing this syndrome was suspected when more common causes, such as a meningeal carcinomatosis, had been excluded by means of CNF analysis and radiological examinations. We review this and other published cases and discuss the possible pathogenesis, as well as the clinical and paraclinical findings in paraplegia following intrathecal chemotherapy. Patients particularly at risk are those who receive intrathecal chemotherapy for over CNS disease rather than as prophylaxis, those who receive several injections and patients who are concomitantly treated with radiotherapy to the brain or systemic high-dose methotrexate or cytarabine.