It is known that cigarette smoking induces leukocytosis and increased genetic instability in normal individuals. Therefore, a retrospective review was conducted of 173 patients with chronic myelogenous leukemia to detect a possible influence of cigarette smoking on initial characteristics at the time of presentation and on the course of this disease. Thirty-nine patients (23%) were smoking 5 cigarettes/d or more at time of diagnosis. Cigarette smoking was significantly related to male sex (P = 0.0005) and younger age at diagnosis (P = 0.02) and smokers tended to have lower leukocyte counts (P = 0.07) than nonsmokers. Cigarette smoking was significantly associated with early blast crisis (P less than 0.0001) and short survival (P less than 0.0001). Other characteristics associated with a poor prognosis included hepatomegaly, anemia, and a high percentage of peripheral blast cells at time of diagnosis. When studied in a multivariate analysis, cigarette smoking remained the strongest prognostic factor for both occurrence of blast crisis (P = 0.0003) and overall survival (P = 0.0001). Other poor prognosis factors found in the multivariate analysis included a high percentage of blasts in the peripheral blood at time of diagnosis and high platelet count. It is possible that cigarette smoke may act as a promoter or cocarcinogen in the transformation of chronic myelogenous leukemia.