Fourteen participating centers registered 33 patients on a Southwest Oncology Group Study of adults with acute non-lymphocytic leukemia (ANLL). Induction consisted of cytosine arabinoside 70 mg/m2 days 1-7 by continuous intravenous (i.v.) infusion, VP-16 50 mg/m2 i.v. over 1 hour days 1-3, and daunomycin 30 mg/m2 i.v. bolus days 1-3. Twenty-five patients (median age 69 years) were evaluable for response. Eleven (44%) achieved a remission marrow but only 8 fulfilled both blood and marrow criteria for complete remission. Of the 11 patients with a remission marrow, there were no patients over 70 years of age. Major coexisting disease data were evaluated. Only 5 patients had no major coexisting disease and 4 of those 5 achieved a remission marrow. The study illustrates and underscores the following problems of remission induction in the elderly: (a) increased susceptibility to the stress of the induction period, with 6 patients (24%) dying before treatment day sixteen; (b) disease resistance to antileukemic therapy with persistent ANLL in 6 patients (24%), despite two induction courses; and (c) hematopoietic stem cell sensitivity in the elderly with marrow regeneration failure documented in 2 patients (8%) following induction. Acute nonlymphocytic leukemia in the elderly has a poor prognosis, and novel therapeutic approaches are warranted.