To characterize the possible role of a dysregulated proliferative capacity of pulmonary fibroblasts in insufficient tissue repair in lungs from patients with pulmonary emphysema, the authors undertook in vitro proliferative studies with pulmonary fibroblasts obtained from lung tissue of patients with emphysema. A comparison was made with fibroblasts from control subjects. The authors determined the in vitro proliferative capacity of fibroblasts at basal culture conditions and after modulation with interleukin-1beta, interferon-gamma, transforming growth factor-beta(1), and basic fibroblast growth factor. Proliferative capacity was determined by measurement of 5-bromo-2-deoxyuridine (BrdU) incorporation. BrdU incorporation by fibroblast cultures from both groups was very similar. Fibroblast cultures from control subjects, however, incorporated more BrdU after incubation with interleukin-1beta than cultures from patients with emphysema (P<.05). On the other hand, transforming growth factor-beta(1) decreased incorporation of BrdU stronger in fibroblast cultures from control subjects than from patients with emphysema (P<.05). Thus, the proliferative capacity of fibroblast cultures isolated from lung tissue of patients with pulmonary emphysema is different from that of control subjects. Although the difference is small, it may be an essential contribution to the development of pulmonary emphysema that only occurs after repeated smoke-induced injury over many years of an individual's life.