The natural history and response to treatment of 46 patients with acute myelogenous leukemia and a pretreatment leukocyte count of 100,000/microliters or higher were reviewed to identify the clinical features and response characteristics to the treatment of this group of patients. While the response rate of 52% was similar to that of patients with lower leukocyte counts, remission durations were shorter and related inversely to the height of the initial leukocyte count and to the number of treatment courses necessary to achieve a complete remission. A high incidence of hemorrhagic deaths was observed during the first 8 days of treatment. These hemorrhages occurred at a time when the leukocyte count was falling secondary to chemotherapy and the platelet count was still greater than 15,000/microliters. Pretreatment coagulation disorders and poor performance status were factors associated with this fatal complication. Antimetabolites to rapidly arrest leukemic cell proliferation and leukapheresis to avoid further leukostatic plug formation may be useful immediate measures to reduce the incidence of these fatal hemorrhages until the underlying pathogenic mechanisms have been elucidated.