The peripheral leukocyte count is an important predictor of mortality. Hence, host and environmental factors influencing the peripheral leukocyte count are of interest. The authors studied 8,635 subjects, aged 30-74 years, who were seen as part of the National Health and Nutrition Examination Survey II in 1976-1980, and sought to assess the relation of age, sex, obesity (body mass index), alcohol use, and various parameters of cigarette smoking to the peripheral leukocyte count using multiple regression analysis. Various parameters of cigarette smoking were statistically significant independent predictors of the peripheral leukocyte count with higher leukocyte counts seen among current smokers, relative to former or never smokers. Among current smokers, a dose-response relation was seen for cigarettes/day and total pack-years smoked. A dose-response relation with pack-years and years since quitting was seen in former smokers. Other variables that were statistically significant independent predictors of a higher peripheral blood leukocyte count were younger age, male sex, increased body mass index, and decreased alcohol consumption. Although the specific cell or cells responsible for these relations are not defined by this analysis, the results support the suggestion that a number of host and environmental factors can influence cellular markers of inflammation.