We investigated the expression of adhesion molecules in circulating neutrophils (lymphocyte function-associated antigen-1 [LFA-1], Mac-1, and L-selectin) and endothelial cells (soluble intercellular adhesion molecule-1[sICAM-1]) in 23 patients with stable chronic obstructive pulmonary disease (COPD), 18 subjects with exacerbated COPD, and 23 healthy volunteers. Also, in these circulating neutrophils, we assessed the expression of two G protein subunits (Galphas and Galphai1/2). Compared with control subjects, patients with stable COPD showed increased expression of Mac-1 (p < 0.001) and lower levels of sICAM-1 (p = 0.002); LFA-1 and L-selectin expression was similar in patients and control subjects. During exacerbations, compared with stable patients, the expression of Mac-1 and LFA-1 was reduced (p < 0.001). Finally, the expression of Galphas (but not Galphai1/2) was also reduced (p < 0.001) in circulating neutrophils of patients with COPD, irrespective of the clinical condition of the patient. These results indicate that in patients with COPD: (1) the expression of some neutrophil adhesion molecules (Mac-1) is abnormal, and that this pattern changes during exacerbations; (2) there may be a form of endothelial dysfunction, as suggested by the low sICAM-1 levels; (3) the expression of G protein subunit (Galphas) in circulating neutrophils is downregulated, irrespective of their clinical conditions. Overall, these results indicate the presence of significant systemic abnormalities in COPD.