Fourteen patients with refractory acute non-lymphocytic leukemia were entered into a dose-seeking trial of combination therapy with etoposide and amsacrine given daily for five consecutive days. There were three complete responses lasting 2 months, 3 months, and 10 months and two transient partial remissions. Dose-limiting toxicities were stomatitis and diarrhea. Prolonged aplasia occurred at the highest doses tested and appeared to result from repetitive doses of the combination given as maintenance. We recommend for induction and consolidation/intensification treatment VP-16, 125 mg/m2, and AMSA, 125 mg/m2, intravenously daily for 5 days. A reduction by at least 50% in the dose of each drug is recommended for maintenance of complete remissions.