High-dose cytosine arabinoside (HD-AraC) has been used in relapsed and refractory cases of acute lymphoblastic leukemia (ALL) and non-Hodgkin's lymphoma (NHL). Sixty-two poor-prognosis ALL patients were treated with HD-AraC between 1983 and 1995 at the Cancer Institute, Chennai, India. Of them, 37 had experienced a relapse, 16 were partial responders (refractory) to the induction regimen, and 9 were high risk due to central nervous system or testicular involvement or total counts above 200,000/mm(3) at presentation. Of the 37 patients with relapses, 22 (59.5 %) achieved complete remission (CR) and 10 had no evidence of disease (NED); of the 16 refractory group patients, 10 achieved CR and 2 had NED; and of the 9 high-risk patients, 5 had NED at the end of the study. The 5-year event;free survival (EFS) values of relapsed, refractory, and high-risk group categories were 21.7%, 12.5 %, and 55.6%, with a mean duration of 41 months, 18 months, and 85 months, respectively. Total alopecia and grade IV myelosuppression were the predominant toxicities. HD-AraC is an effective drug in the treatment of relapsed and refractory acute leukemias and can overcome relative drug resistance in high concentrations.