Candoxatril (UK-79300) is the orally-active prodrug of candoxatrilat (UK-73967), the active enantiomer of (+/-)candoxatrilat (UK-69578), a potent neutral endopeptidase (NEP) inhibitor. This article describes the rationale behind the use of such a drug in the treatment of chronic heart failure in man. It further describes the pharmacokinetics and pharmacodynamics of candoxatril in normal healthy individuals and in patients with chronic cardiac failure. In addition, we describe the initial results comparing candoxatril with furosemide and captopril in human heart failure.