Background: The efficacy of ACE-inhibitor therapy is well documented in the treatment of chronic heart failure. As pharmacological mechanisms of ACE-inhibition and angiotensin II AT1-receptor-antagonists differ, an additional positive effect concerning left ventricular function can be expected in combining both classes of drugs. Methods: Twenty patients Ž . Ž . 64.9" 8.5 years with advanced chronic heart failure NYHA class III receiving long-term medication with digitalis, diuretics Ž . and ACE-inhibitors were randomized to either eprosartan 540 " 96 mgrday or placebo, according to a blinded protocol. Hemodynamic measurements by impedance cardiography were performed at baseline and after 8.85" 1.5 days of study medication treatment. Results: Additional treatment with eprosartan resulted in a higher cardiac output than in the control Ž . Ž group P-0.05 . While in the active treatment group cardiac output increased significantly from baseline 2.27᎐3.24 lrmin, . Ps 0.039 , there was no change in the control group. Conclusions: The additional treatment with the AT1-receptor antagonist eprosartan, given to severe heart failure patients, who received digitalis, diuretics and ACE-inhibitors, resulted in a beneficial effect by increasing cardiac output. This effect may be due to eprosartan's additional property of blocking the autocrine interaction of locally and not ACE-generated angiotensin II with their respective vascular and myocardial AT1-receptors as well as the influence on prejunctional AT1-receptors located on sympathetic nerve terminals. ᮊ