One-hundred and fifty-one adults with acute non-lymphocytic leukemia (ANLL) were entered into an Eastern Cooperative Oncology Group protocol (EST-1473) comparing twice daily cytosine arabinoside and thioguanine (AT) with weekly cyclophosphamide, cytosine arabinoside, and methotrexate (CAM) for remission induction. Of 111 evaluable patients, 16 treated with CAM and 16 treated with AT entered complete remission (CR) on their initial therapy and 5 additional patients entered CR on crossover for a total of 37 or 33% of the evaluable patients. Of the 71 patients who survived three weeks or longer, the overall CR rate was 52%. Cytochemical studies were performed on 85% of the evaluable cases, Minor disagreements between morphologic subtypes of ANLL occurred in 50% of cases. There was no difference in response rates between the major subtypes of ANLL regardless of whether the investigator's diagnosis or the cytochemical reference laboratory diagnosis was used. The median survival of all evaluable patients was 4.9 weeks; those patients who responded with a CR had a median survival of 60 weeks, while those who did not have a median survival of less than 3 weeks. Age less than 60, ambulatory performance status, or fewer than 50% marrow blasts were also associated with a better response rate and longer survival. CAM had more severe mucositis and vomiting associated with it than did AT, but toxicities were otherwise comparble. Weekly CAM and AT appear to be equally effective regimens in the treatment of ANLL.