Twenty-three refractory and/or relapsing acute non-lymphoid leukemia patients were treated with a combination of methotrexate (MTX) and asparaginase (Aase) slightly modifed from that recently proposed by Capizzi et al. Patients received MTX on day 1, followed by Aase 24 hours later; the two day course was repeated weekly. The starting dose of MTX was 60 mg/m2 and was increased by 50% at each course to maximum toxicity. The dose of Aase was kept constant at 10,000 u/m2. Twelve patients achieved complete remission lasting 3 to 58 weeks, with 8 patients surviving more than 30 weeks. Toxicity has been remarkably mild with the major problem being hypersensitivity to Aase.