OBJECTIVE: To investigate possible mechanisms resulting in pulmonary hypertension (PH) in patients with congenital heart disease (CHD). METHODS: Thromboxane B2/6keto Prostaglandin F1a (TXB2/6-K-PGF1a), Von Willebrand factor (VWF: Ag) and tissue plasminogen activator (tPA) plasma levels were measured. Changes in pulmonary vascular endothelial cells were assessed with light and electron microscopy. Ninety-nine children with CHD were divided into 3 groups according to pulmonary vascular resistance (PVR) (Group Ⅰ: PVR≤3.5 wood's unit; Group Ⅱ: PVR 3.5～5 wood's unit; Group Ⅲ: PVR>5 wood's unit). RESULTS: TXB2/6-K-PGF1a and VWF:Ag increased significantly in PH, and varied in different PH groups (P<0.05). There was a positive association between PVR and VWF: Ag (r=0.89, P<0.05) and between pulmonary artery resistance (PAR)and VWF: Ag (r=0.82, P<0.05). The levels of tPA in PH did not differ from normal. With the progressive changes on the light microscopy, the increases in the volume density of rough endoplasmic recticulum and microfilament bundles on the transmission electron microscopy were more significant and the immunostain for VWF: Ag was more intense. CONCLUSIONS: The functional and structural changes of endothelial cells are important in the pathogenesis of PH secondary to CHD. The experiments provide a theoretical basis for the modification of PH secondary to CHD with drug therapy.