In contrast to the effects of cigarette smoke on T-lymphocyte subsets in the airways, it has not yet been determined whether smoking has immunomodulatory effects on surface antigens of peripheral blood T-lymphocytes and, if that is the case, whether these effects differ in smokers with and without chronic obstructive pulmonary disease (COPD). The present authors have, therefore, examined the expression of the surface activation marker CD28, the levels of cytotoxic effector lymphocytes (CD27-/CD45RA+) and the expression of the lung type (Tc)1-specific chemokine receptor CXCR(3)+ on peripheral blood CD8+ T-lymphocytes. The present authors have also studied the chemotactic activity of CD8+ T-lymphocytes on monocyte chemotactic protein (MCP)-1 and compared 13 nonsmoking controls, 12 smokers with COPD and 14 smokers without airflow limitation. There was a decrease in the total count of CD8+ T-cells and an increase in the CD4+/CD8+ ratio in smokers with COPD compared with smokers without COPD and controls. Expression of the Tc1-specific chemokine receptor CXCR(3)+ by CD8+ T-cells was increased in smokers with COPD compared with smokers without COPD and controls. The expression of activated and of cytotoxic effector CD8+ T-cells in smokers with and without COPD showed an increase compared with controls. CD8+ T-cells from smokers with and without COPD showed a decrease in chemotactic activity to MCP-1 compared with controls. In conclusion, chronic obstructive pulmonary disease may be a systemic immunomodulatory disease associated with the modification of surface antigens in blood CD8+ T-lymphocytes.