One-hundred and sixty-one of 378 previously untreated patients with acute myelogenous leukemia (AML) failed to enter complete remission with a combination of anthracycline, cytosine arabinoside, vincristine, and prednisone between 1973 and 1979. Thirty-six of the failing patients (22%) were considered chemotherapy failures. As in the past, the remainder failed largely because of death from infection. However, despite the routine use of prophylactic platelet transfusions, hemorrhage was a major cause of death in 33%. Thirty-seven percent of the fatal infections were due to fungi and the incidence of fungal infection was as high during the second week of treatment as later. Age greater than 50 yr predisposed to fatal infection but not chemotherapy failure, while the presence of an antecedent hematologic disorder increased the risk of both fatal fungal infection and resistance to chemotherapy. Patients with an initial white blood cell count of greater than or equal to 25000/microliter were more likely to die of hemorrhage at all times during treatment. Improvement in supportive care remains crucial if improved complete rates are to be forthcoming in previously untreated patients.