Dendritic cells (DCs) play an unsettled role in chronic obstructive pulmonary disease (COPD) pathogenesis. Two main blood subsets, myeloid (m) and plasmacytoid (p) DCs, have been identified in humans. Phenotype and frequency of circulating DC subsets were assessed by multi-parametric flow cytometry in 28 COPD patients and 30 healthy controls (15 never smokers and 15 smokers). Proportion and absolute number of pDCs were significantly reduced in COPD patients in comparison with never smokers (p<0.001 and p<0.003) along with a marked increase of the mDC/pDC ratio (p<0.001). Analysis of peripheral lymphocyte subsets showed that the naive/memory T cell ratio was significantly reduced in COPD patients in comparison with never smokers (p<0.001). Similar perturbations in the distribution of DCs and T cells also occurred in control smokers. This study is the first report of an imbalance of blood DCs in COPD. Influence of smoking and clinical relevance of these findings are discussed. Copyright © 2010 Elsevier Inc. All rights reserved.