VEGF is an endothelial specific mitogen which is highly expressed in the lung, primarily in distal airway epithelial cells. In many organs VEGF is associated with increased vascular permeability. We and others have shown that VEGF is upregulated by hypoxia and downregulated by dexamethasone and hyperoxia. Inflammatory cytokines also have been shown to increase VEGF. The role(s) of VEGF in the lung is not yet known. We wondered whether VEGF was associated with acute respiratory disease in low birthweight premature infants. Tracheobronchial aspirates were collected from 37 intubated infants at 12-24 hours (Day 0) and on days 4 and 10. Mean birthweight was 788 grams(500-1224) and mean gestational age was 27 weeks (23-30). VEGF was detected in 94% of the samples (detection limit 15 pg/ml). VEGF concentrations on days 4 and 10 were significantly increased over Day 0. Day 0 = 101 ± 96(pg/ml, mean ± SD); Day 4 = 450 ± 318; Day 10 = 488 ± 307. There was no correlation with birthweight, gestational age, FIO2, severity of respiratory disease or outcome at 28 days. There was no correlation with the levels of the inflammatory cytokines LTB4 and IL-8 or with the cellularity of the sample. No infant received steroids before Day 10. The lack of correlation with with these factors suggests that VEGF was not involved in the pathogenesis of the acute respiratory diseases in these infants. It is possible that the rise in VEGF over the first 4 days of life was a normal developmental process, but that interpretation is limited since only intubated infants could be studied. Future studies in infants with chronic lung disease will determine whether VEGF is associated with later respiratory problems.