Rationale: Fibroblasts are believed to be the major cells responsible for the production and maintenance of extracellular matrix. Alterations in fibroblast functional capacity, therefore, could play a role in the pathogenesis of pulmonary emphysema, which is characterized by inadequate maintenance of tissue structure. Objectives: To evaluate the hypothesis that deficient fibroblast repair characterizes cells obtained from individuals with COPD compared to control subjects. Measurements and Main Results: Fibroblasts were cultured from lung tissue obtained from individuals undergoing thoracotomy and were characterized in vitro. Fibroblasts from individuals with COPD, defined by reduced FEV₁, manifested reduced chemotaxis toward fibronectin and reduced contraction of three-dimensional collagen gels, two bioassays associated with fibroblast repair function. At least two mechanisms appear to account for these differences. PGE, a known inhibitor of fibroblast repair functions, was produced in increased amount by fibroblasts from COPD subjects, which also expressed increased amounts of the receptors EP2 and EP4, both of which signal through cyclic AMP. Incubation of fibroblasts with indomethacin or with the PKA inhibitor KT-5720 partially restored COPD subject fibroblast function. In addition, fibroblasts from COPD subjects produced more TGF-1, but manifested reduced response to TGF-1. The functional alterations in fibroblasts correlated with both lung function assessed by FEV₁ and, for the data available, with severity of emphysema assessed by DLCO. Conclusions: Fibroblasts from individuals with COPD have reduced capability to sustain tissue repair and suggest this may be one mechanism that contributes to the development of emphysema.