Fifteen patients with acute nonlymphocytic leukemia (ANLL) who either had a relapse after a previous complete remission (nine patients) or progressive disease after initial induction attempts with combination chemotherapy (six patients) were treated with 5-azacytidine. Five patients (33%) achieved a complete remission (CR); of these, three had a relapse and died 30, 35, and 38 weeks after 5-azacytidine therapy was begun. Two patients are still alive at 39 and 138 weeks. Chromosomes were analyzed at the time of diagnosis; ten patients had a normal karyotype and five had an abnormal karyotype. Three of the five CR patients had an abnormal karyotype initially. Two of these individuals had a translocation of chromosomal material from a No. 8 chromosome to a No. 21 chromosome, t(8;21); this particular translocation has been associated with a better prognosis than have other types of chromosomal abnormalities in patients with ANLL. Even when abnormal chromosomes are present, 5-azacytidine can induce complete remission in patients with previously treated ANLL.