We report a single institution sequential trial of two maintenance treatment regimens for patients with acute myelogenous leukemia (AML). A total of 175 consecutive patients with AML received initial remission induction therapy with high-dose cytosine arabinoside (ara-C) and glucocorticoids. For the initial 63 patients (group A), the control population, planned maintenance treatment was with conventional-dose ara-C given over 4 days for up to 18 months. The subsequent 107 patients (group B) had planned maintenance therapy of up to 6 courses of daunorubicin, ara-C and prednisone and daily cis-retinoic acid for up to two years. The presenting features of group A and B patients were similar as were the response to remission induction, 60 and 52%, respectively. Severe neurological toxicity was encountered once after high-dose ara-C; no drug-related deaths occurred during maintenance treatment. Median duration of remission for group B patients was 9.9 months compared with 5.5 for group A (p = 0.0685). Median survival duration for the two groups was similar, 9.1 months for group A and 10.4 for group B. Survival of patients in group B who attained a complete remission was significantly better than that of patients in group A (p = 0.0439). The studies confirm our initial experience with remission induction using single agent high-dose ara-C and suggest a positive role for maintenance therapy in AML.