High dose cytosine arabinoside (ARA-C) has produced long term relapse free survival in 26% to 49% of patients when used as consolidation therapy of acute non-lymphocytic leukemia (ANLL) in first remission. However, the optimal consolidation regimen has not been defined. In this pilot study we attempted to confirm and extend our previous studies of high dose consolidation therapy by administering two cycles of consolidation chemotherapy to patients with ANLL in first remission. The first cycle was high dose ARA-C 3 gm/m2 over 1 hour every 12 hours for 12 doses followed by daunorubicin 45 mg/m2/day for three days. The second cycle was etoposide 75 mg/m2/day for 10 days and mitoxantrone 12 mg/m2/day for three days. Twenty-three patients received high dose consolidation chemotherapy, 13 of whom received the proposed two cycles. The major reason for not receiving the planned second consolidation cycle was life threatening toxicity, primarily fungal infection, during the first consolidation cycle. By actuarial estimate, 46% of patients receiving consolidation chemotherapy were projected to be relapse free at 36 months. There were no deaths during consolidation. Survival was not improved in patients receiving etoposide and mitoxantrone as the second cycle of consolidation therapy as compared to patients receiving only one cycle of consolidation therapy.