Elevated plasma concentrations of big endothelin-1 (big ET-1) are related with severity and prognosis in patients with heart failure, and N-terminal pro-brain natriuretic peptide (NT-proBNP) is a marker of ventricular remodeling. The purpose of this study was to investigate the relationship between plasma levels of big ET-1 and NT-proBNP, and between the former and ventricular function. We studied 103 patients with heart failure (75 men, mean age 63 [13] years). Each participant completed a questionnaire and underwent Doppler echocardiographic study to measure ejection fraction (EF), mitral flow propagation velocity (Vp) and atrioventricular plane displacement (AVPD). Blood samples were also taken to determine plasma levels of big ET-1, aldosterone and NT-proBNP. For the whole population big ET-1 concentration was 1.03 [0.75] fmol/m, NT-proBNP 619 (307-1328) pg/mL, aldosterone 168 [102] pg/mL, EF 37 [10], Vp 37 [11] cm/s, and AVPD 8.0 [1.7] mm. Plasma big ET-1 correlated positively with plasma NT-proBNP (r=0.50, P<.0001). However, a negative correlation was found between big ET-1 and EF (r=-0.30, P<.01), Vp, (r=-0.30, P<.01) and AVPD (r=-0.21, P<.05). When ET-1 levels were divided into quartiles and the corresponding NT-proBNP, EF, Vp and AVPD values were compared, we found significant differences (ANOVA P<.0001, P<.01, P<.05 and P<.05, respectively). Plasma levels of big ET-1 correlated positively with NT-proBNP levels and inversely with EF, Vp and AVPD. These findings help clarify the relationships between ventricular function and the neurohormonal activation involved in heart failure, and may aid the search for therapeutic interventions.