Congenital diaphragmatic hernia (CDH) is a congenital disorder, complicated by pulmonary hypoplasia (PH) and pulmonary hypertension. Hypoplastic lungs have fewer and smaller airspaces than normal, with thicker interalveolar septa; the adventitia and media of pulmonary arteries are thickened, and the total size of the pulmonary vascular bed is decreased compared to normal. Although histological abnormalities in PH have been described, less is known about the underlying molecular mechanisms. Therefore, we have investigated a series of proteins, known to be involved in angiogenesis, including von Hippel-Lindau protein (pVHL), hypoxia-inducible factor-1a (HIF-1a), vascular endothelial growth factor (VEGF), fetal liver kinase 1 (Flk-1), and endothelial and inducible nitric oxide synthase (eNOS, iNOS) by immunohistochemistry on paraffin-embedded lung tissue of CDH patients (n = 13), patients with lung hypoplasia due to other causes (n = 20), and normal controls (n = 33). pVHL was expressed more frequently in the arterial smooth muscle cells of CDH lungs compared with both other groups. Furthermore, HIF-1a was expressed less frequently in the endothelium of arteries, veins, and capillaries of CDH lungs as compared with both other groups. No differences were observed in the expression patterns of VEGF, Flk-1, eNOS, and iNOS between the different groups. Our data suggest a role for pVHL and HIF-1a in normal and abnormal pulmonary angiogenesis. The differential expression of these proteins may provide a molecular basis for the histological differences observed in the lung vessels of patients with CDH.