High dose cytosine arabinoside (HD-AraC) was evaluated 1) as remission induction therapy for refractory acute leukemia and high risk AML, 2) as augmentation therapy for acute leukemia, and 3) as conditioning therapy prior to allogeneic bone marrow transplantation for acute leukemia. Seven of 10 patients with refractory AML achieved complete remission with a median time to response of 32 days. Four of 8 patients with previously untreated, high risk AML had a favorable therapeutic outcome with 3 patients achieving complete remission and 1 patient converting to a chronic myeloproliferative disorder. Median time to response was 36 days. Three of 8 patients with refractory ALL achieved partial remission with response also demonstrated for 5 of 6 patients with meningeal leukemia. Seven patients with previously untreated AML, predicted to be at high risk of failing conventional remission induction therapy because of persistent marrow hypercellularity after 6 days, received augmentation therapy with HD-AraC. Four patients achieved complete remission with a median time to response of 36 days. Augmentation therapy was also employed for refractory AML and refractory ALL. HD-AraC was included as part of a conditioning regimen for allogeneic bone marrow transplantation to provide initial cytoreductive/cytoablative therapy and to provide therapy directed at leukemic sanctuary sites. Treatment was well tolerated with the major toxicities being myelosuppression, nausea, vomiting and diarrhea. Neurologic toxicity, manifested as confusion and/or cerebellar ataxia occured in 13% of patients and was reversible in all but one instance. Other toxicities were conjunctivitis and/or photophobia (22%), hepatic enzyme abnormalities (13%), rash (17%), and drug-related fever (2%).