5-azacytidine (5-AZA) and carboplatin (CBDCA) are two agents which have demonstrated antileukemic activity in a number of phase I-II trials. Their mechanisms of action and pharmacology related to cell resistance suggested suitability for combination therapy. The aim of this pilot was to evaluate the effects of this combination in the treatment of patients with relapsed/refractory acute leukemia. A total of 21 patients was enrolled. 5-azacytidine, at doses ranging from 50-150 mg/m2/day, was administered as a 2-hr infusion for 5 consecutive days. On day 3, patients began a 5-day course of CBDCA given as a 24-hr continuous intravenous infusion of 250 mg/m2/day. There were no complete remissions with this regimen. Although there were three partial responses, these were generally of short duration. Nonhematologic toxicities were mild. No correlation was seen between response and serum platinum levels. These results demonstrate that the 5-AZA/CBDCA combination is ineffective therapy for heavily pretreated patients with acute leukemia.