Forty-seven patients with poor-prognosis myeloid leukemias received induction therapy with high-dose cytosine arabinoside (HDara-C), 1.5–3.0g/m2for 8–10 doses, and mitoxantrone (DHAD), 12–15 mglm2for 3 doses. Complete remissions were achieved in 21 [45%, 95% confidence interval (CI) 30.2–59.9%]of the patients, including 11 of 14 with acute myelogenous leukemia (AML) in first relapse (79%, 95% CI 49.2–95.3%), 4 of 8 with refractory anemia with excess blasts in transformation (RAEBiT) (50%, 95% CI 15.4–84.6%), and 4 of 6 (67%, 95% CI 22.3–95.7%) previously untreated elderly AML patients. Patients with secondary AML and advanced chronic myelogenous leukemia had a very low response rate. The incidence of reversible toxicity was low and only 3 treatment-related deaths occurred. After reinduction, 8 of 9 AML patients≤60 years of age were ultimately able to undergo intensive therapy and either autologous 4-hydroperoxycyclo-phosphamide-purged bone marrow (7 patients) or peripheral blood stem cell (1 patient) transplantation with satisfactory hematological recovery. We conclude that HDara-C and DHAD is an effective antileukemic regimen in selected AML and RAEBiT patients, and that its use may allow subsequent successful autologous BMT in appropriate patients.