In order to characterize the changes of five neurohormones in pediatric patients with varying degrees of congestive heart failure (CHF) secondary to congenital heart disease (CHD), we measured plasma neurohormone levels by using radioimmunoassay or high-performance liquid chromatography in 81 subjects including 13 normal children and 68 pediatric patients with CHD. Patients with CHF (n=27) had elevated levels of big endothelin-1 (big ET-1) (29.5+/-1.6 vs. 18.1+/-2.1 pg/ml, p<0.001), endothelin-1 (ET-1) (17.9+/-1.7 vs. 7.8+/-1.7 pg/ml, p<0.001) and norepinephrine (505.6+/-65.6 vs. 219.6+/-23.3 pg/ml, p<0.01) as compared with healthy control subjects (n=13). Plasma norepinephrine levels (505.6+/-65.6 vs. 230.0+/-8.0 pg/ml, p<0.001) and atrial natriuretic peptide (35.5+/-4.2 vs. 7.6+/-0.6 pg/ml, p<0.001) in the 27 patients with CHF were significantly higher than in the 41 patients without CHF. There was also a highly significant stepwise increase in big ET-1, atrial natriuretic peptide and norepinephrine according to the severity of heart failure. Our results suggest that increased circulating neurohormonal activity in CHD relates to the presence and clinical severity of heart failure in children. Plasma levels of big ET-1 and ET-1 were not only significant markers of CHF but also correlated well with the severity of CHF in CHD with left-to-right shunt.