Patients with leukemias that have relapsed from previous therapies have a low cure rate. Hence the need to discover new antileukemic agents. Tezacitabine is a nucleoside analogue with equivalent or even superior activity when compared with ara-C in leukemic cell lines. It has shown significant antitumor activity in vitro and in vivo tumor models. Several phase I studies with various dosing schedules have been conducted in solid tumors where the DLT is mainly myelosuppression, usually a favorable feature for development of leukemia. In a phase I study in hematological malignancies, we used Tezacitabine as a bolus infusion daily x 5. The DLT consisted of grade 3 CNS toxicities and mucositis in 3/6 patients. The study is ongoing and we are currently evaluating a dose level of 7.5 mg/m2 as possible MTD. However, in view of the fact that tezacitabine is a cell cycle specific agent with a short terminal plasma half-life of 2 to 6 hours, a continuous infusion dosing schedule may enhance the activity and reduce the incidence of adverse effects of tezacitabine.