25 consecutive leukemia patients (21 AML, 4 ALL) with either primary resistance (n = 22) or resistant relapse (n = 3) of all FAB-subtypes were treated with 1 or 2 cycles of ID-ara C (1 g/m2 i.v. q 12h days 1-6) and AMSA (120 mg/m2 i.v. days 5-7). Patients reaching CR received 1 cycle of intensive consolidation using ara C 3 g/m2 i.v. q 12 h days 1-4 and AMSA 120 mgm2 day 5. Two patients received an allograft thereafter and are still alive and in CCR. CR was achieved in 12/25 patients (48%), in 10 after 1 cycle of induction and in 2 after 2 cycles. 10/22 patients with primary resistant disease reached CR, and 2/3 with resistant relapse. 9 patients remained refractory (36%) and 4 died during hypoplasia (16%) Median DFS of the 12 responders was 2.9 months and median survival from time of CR 8.9 mo. Median overall survival of responders and non-responders was 6 mo from time of resistance. The survival advantage of responding patients (n = 12) as compared to non-responders (n = 13) was 10.7 vs. 3.2 mo (p = 0.002). Toxicity of chemotherapy was acceptable. 1 patient experienced pulmonary edema due to ara C, 2 patients developed life threatening systemic fungal infections, one of whom died while in CR.