The changes of adrenomedullin (ADM), endothelin-1 (ET-1) and nitric oxide (NO) lev-els before and after operation in congenital heart disease (CHD) associated with pulmonary hyper-tension (PH) were observed in order to investigate their role in CHD with PH and their clinical sig-nificance. The CHD patients were divided into 3 groups according to pulmonary artery systolicpressure (PASP): Non-PH group: PASP≤30 mmHg (n = 11); mild-PH group: PASP 3t - 49mmHg (n= 10); moderate or severe-PH group: PASP≥50 mmHg (n=- 12). The control groupconsisted of 15 health children. Plasma ADM, ET-1 and NO levels were determined by radioimmu-noassay and colorimetry methods. The correlation between ADM and ET-1, NO, PASP was ana-lyzed. The changes in plasma ADM, ET-1 and plasma NO on the 7th day after operation among thegroups were compared. The results showed that plasma ADM levels in non-PH group were signifi-cantly higher than that in control group (P＜0.05), but there was no significant difference in ET-1and NO levels between the two groups (P＞0.05). ADM and ET-1 levels in mild-PH group weresignificantly elevated as compared with those in non-PH group (both P＜0. 05), but NO levelswere decreased (P＜0. 05). ADM and ET-1 levels in moderate or severe-PH groups were increasedas compared with those in mild-PH group (both P＜0.01), but NO level significantly declined (P＜0.05). On the 7th day after operation, plasma ADM and ET-1 levels in PH group were signifi-cantly decreased (P＜0.05, P＜0.01) as compared with those before operation, but there was nosignificant difference in NO levels (P＞0.05). But NO levels in non-PH group were significantlyincreased (P＜0.05). Plasma ADM levels in CHD were positively correlated with PASP and ET-1(r=0.77, P＜0.01; r=0.82, P＜0.01), negatively correlated with NO (r=-0.56, P＜0.05).It was concluded that during the progression of PH in the cases of CHD, plasma ADM, ET-1 andNO might play an important role in the development of PH. The increased ADM may represent acompensatory mechanism. It can interact with NO and ET-1 to regulate pulmonary circulation inthe pathophysiology of PH with CHD. ADM may be involved in the defence mechanism against fur-ther increase of pulmonary arterial pressure. ADM could be used as a reliable indicator of the sever-ity of CHD associated PH.