Smoking is a recognized major risk factor for the development chronic obstructive pulmonary disease (COPD). COPD is characterized by abnormal inflammatory response of the airways to various stimuli, in which T-lymphocytes, macrophages and neutrophils are involved. The objective of this study was to assess the role of cytotoxic CD8+ lymphocytes in the inflammatory process associated with COPD. In particularly, expression of perforin and the cytotoxic activity of cytotoxic CD8+ lymphocytes were examined. The study included 36 male smokers with COPD, 25 male smokers without COPD and 10 male healthy non smokers. Cytotoxic CD8+ cell count in induced sputum was determined by immunocytochemical methods using monoclonal anti-CD3-FITC and anti-CD8-FITC antibodies. The expression of perforin was assessed by flow cytometry using anti-perforin-FITC antibody. The cytotoxic activity of CD8+ lymphocytes was assessed in their cultures with appropriate target-cells (K562). The percentage and the absolute number of cytotoxic CD8+ cells were significantly higher in smokers with COPD compared to both smokers without COPD (P = .005) and healthy non smokers (P = .0001). Smokers with COPD showed also significantly higher levels of perforin expression and cytotoxic activity of CD8+ lymphocytes in comparison to the other two study groups (P < .05). The results of this study indicate that CD8+ cells in induced sputum obtained from patients with COPD are more cytotoxic in relation to those obtained from smokers without obstruction. It is considered likely that their cytotoxic activity is a result of increased perforin release.