Vascular endothelial growth factor (VEGF) plays multifunctional roles in both the development of vasculature and the maintenance of vascular function. A decrease in VEGF reduces angiogenesis and induces apoptosis of vascular endothelial cells. Inhibition of the VEGF receptor causes endothelial cell apoptosis and emphysema. We postulated that VEGF concentrations might be reduced in patients with chronic lung diseases. The level of VEGF was evaluated by enzyme-liked immunosorbent assay in bronchoalveolar lavage fluid (BALF) from normal smokers, nonsmoking volunteers, idiopathic pulmonary fibrosis, pulmonary fibrosis associated with a connective tissue disease, and sarcoidosis. The isoforms of VEGF in BALF were determined by high-performance liquid chromatography. VEGF in nonsmoking volunteers was detectable at a high concentration. In contrast, VEGF in most of the normal smokers was below the detectable limit. The VEGF found in nonsmoking volunteers BALF was VEGF165. VEGF was significantly decreased in idiopathic pulmonary fibrosis, pulmonary fibrosis associated with a connective tissue disease, and sarcoidosis compared with nonsmoking volunteers. The smoking patients showed a further decrease in VEGF. These data suggest that the decrease in VEGF in smokers and patients with chronic lung diseases may reduce angiogenesis and induce apoptosis of vascular endothelial cells.