Stimulated neutrophils from subjects with various inflammatory tissue-destructive conditions, such as periodontal, pulmonary, gastrointestinal, and cardiovascular diseases, generate more oxygen radicals and proteases, implicated in tissue destruction, than neutrophils from healthy persons. Cigarette smoking aggravates these diseases. The aim of our study was to investigate the effect of cigarette smoking on the priming capacity of tumor necrosis factor-alpha, measured as generation of radicals from stimulated neutrophils, in smoking and non-smoking subjects with or without periodontitis. The priming effect was higher in neutrophils from smokers. In the group with periodontitis, smoking caused an even greater increase in the generation of radicals, indicating an additive effect of this local disease. The membrane expression of CD11b, CD15, and CD63 was significantly higher on neutrophils from smokers, indicating upregulated neutrophil functions. This increased priming effect of tumor necrosis factor-alpha in smokers subjects could be of importance in the aggravation of tissue-destructive inflammatory diseases.