One-hundred-fifty-four patients with acute leukemia and extensive prior chemotherapy were treated with 5-Azacytidine and evaluated according to five different schedules. One-hundred-twenty patients received adequate trials; 34 patients died within 14 days of onset of treatment. Nine patients achieved a complete remission (CR) and two achieved a partial remission. Although two of the treatments have a higher remission rate, the data were not statistically significant. The median time to CR was 48 days (range 21-173). The median duration of CR was 65 days (range 39-369). There was no difference in response rate according to cell type. The median age of responders was 31 years, and 39 years for nonresponders. Proportionately there were more women among responders (5M/6F) and more men (70M/39F) among nonresponders. At onset of therapy the median leukocyte counts were similar between responding (5.4 X 10(3)) and nonresponding (5.7 X 10(3)) patients, but the proportion of leukemic cells was significantly higher among nonresponding patients (46% vs. 7%). Toxicities included nausea, vomiting, diarrhea, skin rash, myalgias, prolonged myelosuppression, hypotension, and central nervous system stupor and/or coma. Lower dose continuous infusion schedules of five-, seven-, and ten-days duration appear effective and were associated with less toxicity.