Cigarette smoking increases the total peripheral blood leukocyte count but its effect on the differential cell count in peripheral blood is largely unexplored. We studied 6138 subjects between the ages of 30 and 74 years who were seen as part of the First National Health and Nutrition Examination Survey in 1971 to 1974 to assess the relationship of current smoking status, number of cigarettes smoked per day, pack-years of smoking, and years since quitting, to the absolute and percent count of neutrophils, eosinophils, lymphocytes, and monocytes in peripheral blood. The relationship of cigarette smoking to the differential cell counts was adjusted for age, race, sex, and obesity by multiple regression. Pack-years smoked, years since quitting, and current number of cigarettes smoked per day were all independent predictors of the absolute neutrophil count and of the absolute lymphocyte count. Number of cigarettes smoked per day was the only smoking variable predictive of the absolute monocyte count and the absolute eosinophil count. When differential cell counts were considered as a percent of total leukocytes, the results were somewhat different. Neutrophils were disproportionately increased by current number of cigarettes smoked per day. Increased cigarette smoking decreased the proportion of white blood cells that were lymphocytes or eosinophils. Other smoking variables had no influence on percent counts for the specific white cell types in peripheral blood. These data suggest that the effect of cigarette smoking on differential cell counts is not uniform and is primarily influenced by current smoking behavior, although long-lasting effects of past smoking are also evident.