The association between leukocyte count and subsequent risk of lung cancer was evaluated in three large cohorts from the United States and Britain. A total of 309 lung cancer events occurred among 28,181 men whose cases were followed-up for 7 to 12 years. In all three cohorts, there was a marked increase in risk of lung cancer with increasing leukocyte count, after adjustment for age and the number of cigarettes smoked per day. The adjusted relative odds in the three cohorts, for a 2000/microliters difference in leukocyte count, were 1.58 (P = 0.0001), 1.29 (P = 0.003) and 1.20 (P = 0.02). These relative odds persisted when current smokers were considered alone, when serum markers of cigarette smoking exposure were adjusted for, and when men with lung cancer events during the first 5 years of follow-up were excluded. The leukocyte count appears to be linked to the pathogenesis of smoking-related lung cancer.