ET-1 is the most potent vasoconstrictor known to date, causing vasoconstriction when bound to the ET_A receptor. Inhibitors of the binding of ET-1 to the ET_A receptor would be of immense value as potential therapeutic agents in the treatment of cardiovascular disorders such as angina and hypertension. We present here the rational design of such an inhibitor, which is arrived at on the basis of a model of the ET-1/ET_A receptor complex proposed by us. The model is found to be consistent with binding and mutagenesis studies of ET-1 as well as of BQ123, a known, potent ET_A-selective antagonist which competes with ET-1 for receptor binding. BQ123 is a peptidic antagonist which is constrained to adopt a definite conformation on account of its cyclic nature. The noncyclic peptide antagonist designed by us also has a unique conformation because it contains two dehydro-Alanine (ΔAla) residues which, on account of their planarity, cause the peptide backbone to bend in a specific and predictable manner. The folding rules for peptides containing ΔAla were derived in our earlier studies. Energy minimization and modelling of the complex of the designed peptide with the ET_A receptor indicate that the antagonist is ET_A-selective and the binding is more stable and more specific as compared to that of BQ123.