Objectives: We investigated the changes in plasma big endothelin (big ET), atrial natriuretic peptide (ANP), and brain natriuretic peptide (BNP) levels during carvedilol therapy in patients with congestive heart failure (CHF). Study design: The study included 20 patients (6 females, 14 males; mean age 57±11 years) with symptomatic CHF. All the patients had sinus rhythm and resting ejection fraction ≤40%. Carvedilol therapy was initiated with a minimum dose (2 x 3.125 mg), which was increased biweekly to reach the maximum tolerable dose. Blood samples were obtained and transthoracic echocardiography was performed before and after three months of a mean carvedilol dose of 42.5±13.6 mg. Big ET, ANP, and BNP levels were assessed and correlations were sought with left ventricular functions and the NYHA (New York Heart Association) functional class. Results: After three months, significant decreases were detected in heart rate (p<0.001), systolic blood pressure (p<0.05), and left atrial diameter (p<0.001), accompanied by a significant increase in left ventricular ejection fraction (EF) (p<0.001), and a remarkable improvement in NYHA class (p<0.05). Significant decreases were observed in ANP, BNP, and big ET levels with carvedilol treatment (p<0.001). Big ET, ANP, and BNP levels showed significant correlations with left ventricular dimensions and systolic functions, and NYHA functional class. Among these, the best correlation was with LVEF (r= -0.498, p=0.001; r= -0.642, p<0.001; r= -0.656, p<0.001; respectively). Conclusion: Carvedilol therapy is associated with decreased BNP, ANP, and big ET levels and with improvements in NYHA functional class and left ventricular systolic functions in patients with CHF.