Phase I/II-studies suggested that mitoxantrone is effective in the treatment of acute leukemia. In this study we have investigated its efficacy in combination with VP-16 in patients with refractory acute myelogenous leukemia. The regimen consists of: mitoxantrone 10 mg/m2/day i.v. from days 1 to 5, VP-16 100 mg/m2/day as short infusion from days 1 to 3. A dosis escalation of VP-16 was attempted. As of August 1985, 27 patients have been enrolled in the study and 21 patients are now evaluable. Of these 21 patients, 6 (28.6%) have achieved complete remission including 3 with primary refractory disease, 2 with early relapse (less than 6 months after CR), and 1 with relapse under maintenance therapy. Two other patients have attained a partial remission. Toxicity was mild and, except one case of early death, no life threatening complications were observed. This combination seems to be an active regimen in refractory acute myelogenous leukemia and its incorporation in front line therapy seems warranted.