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Endothelial cell damage is characteristic for respiratory distress syndrome and development of chronic lung disease. Vascular endothelial growth factor (VEGF) is an endothelial mitogen that takes part in the growth and repair of vascular endothelial cells. We measured VEGF in 189 tracheal aspirate samples (TAF), and in 24 plasma samples from 44 intubated preterm infants (gestational age, 27.3 ± 2.0 wk; birth weight, 962 ± 319 g) during their first postnatal week. VEGF in TAF increased from 25 ± 12 pg/ml (mean ± SEM) on Day 1 to 526 ± 120 pg/ml on Day 7 (mean concentrations, 106 ± 25 pg/ml on Days 1 to 3 and 342 ± 36 pg/ml on Days 4 to 7). In plasma, mean concentration of VEGF during the first week was 48 ± 6 pg/ml, with no increase observed. In TAF, higher VEGF was found in patients born to mothers with premature rupture of the membranes, or chorionamnionitis, whereas preeclampsia of the mother was associated with lower VEGF (all p < 0.05). In TAF, no correlations existed between VEGF and gestational age or birth weight, but a correlation existed between lecithin/sphengomyelin ratio and VEGF (p < 0.05). During Days 4 to 7 patients developing bronchopulmonary dysplasia (BPD) had lower VEGF in TAF than did those surviving without BPD (235 ± 31 versus 383 ± 50; p < 0.05). VEGF increased rapidly in the lungs of the preterm infant during the first days of life. VEGF may be indicative of pulmonary maturity and may participate in pulmonary repair after acute lung injury.