Progress in clinical intrathecal chemotherapy has been slow, and a number of new problems have been encountered. The most significant recent developments include the: 1) success of adjunctive intrathecal chemotherapy in the prevention of meningeal leukemia; 2) recognition and characterization of a necrotizing leukoencephalopathic reaction associated with intrathecal methotrexate therapy; 3) demonstration of the efficacy of intraventricular chemotherapy via an Ommaya reservoir; 4) delineation of the clinical pharmacology of intralumbar and intraventricular methotrexate; and 5) identification of an urgent need for new drugs and techniques for intrathecal administration.