Microvesicles (MVs) released from almost all cells are recognized as cell communication tools. MVs have been investigated in several inflammatory diseases but poorly in biological fluids like bronchoalveolar lavage (BAL) of smokers. The purpose of this study was to investigate the presence and source of MVs in BAL of smokers with and without chronic obstructive pulmonary disease (COPD) compared with nonsmoking controls. Using flow cytometry in BAL, we detected endothelial and alveolar macrophage (AM)-derived MVs and found a higher number of AM-MVs in the BAL of smokers with COPD than in smokers without COPD and nonsmokers, which correlated with the pack-years ( r = 0.46; P = 0.05) and with the degree of airway obstruction measured by the forced expiratory volume in 1 s percent predicted ( r = −0.56; P = 0.01). Endothelial and alveolar macrophage-derived MVs are present and measurable in human BAL fluid. In response to smoking and to the development of COPD, inflammatory signals in AM-derived MVs can be quantified, and their numbers are related to the pack-years and the decrease in lung function. These results open the opportunity for future investigation of these microvesicles as biomarkers and possible mechanistic guides in COPD.