Vascular endothelial growth factor (VEGF) is a potent angiogenic agent that is expressed by epithelial cells in the mature lung of various animal species. We hypothesized that VEGF levels in lower respiratory tract secretions may vary with age or with lung inflammation in human beings. We measured VEGF165 in bronchoalveolar lavage fluid (BALF) from normal volunteers (NVs) of varying age and from patients with cystic fibrosis (CF), sarcoidosis, or idiopathic pulmonary fibrosis (IPF). A considerable gradient in VEGF levels was found with relatively high VEGF concentrations in BALF as compared with serum VEGF. VEGF levels were 303 +/- 34 pg/mL (mean +/- SEM) in serum samples from patients with CF (N = 9) versus 122 +/- 16 pg/mL for the comparable, youngest group of NVs (P < .01). BALF VEGF concentrations were 165 +/- 17 pg/mL for CF upper lobe BALF (N = 9), 140 +/- 17 pg/mL for CF lower lobe BALF (N = 9), and 235 +/- 24 pg/mL for young adult NVs (N = 29). Serum VEGF levels did not differ significantly between NVs and patients with interstitial lung disease, but mean BALF VEGF levels declined significantly with advancing age in NVs and were significantly depressed in patients with IPF (32 +/- 6 pg/mL) as compared with all other groups, including the oldest group of NVs (134 +/- 13 pg/mL, P < .0001). We conclude that a considerable gradient in VEGF concentration exists from epithelial bronchoalveolar surface fluid to serum. Concentrations of VEGF in lower respiratory tract secretions vary with age and are significantly depressed in IPF.