The synthesis and biological activities of angiotensin II (AII) analogues are described and compared to the literature. D-Amino acid substitution was employed to search for novel AII antagonists that would also display reduced partial agonist activity. Substitution of D-amino acids into the interior positions 2-7 of [Sar1,Ile8]-AII gave rise to inactive compounds or weak antagonists. Substitution of D-amino acids into position 8 gave rise to potent antagonists in vivo including [Sar1,D-Phe8]-AII 8, [Sar1,D-(alpha Me)Phe8]-AII (35), [Sar1,D-Trp8]-AII (32), [Sar1,D-Phg8]-AII (29), [Sar1,D-Peg8]-AII (30), and [Sar1,D-Phe8]-AII-NH2 (31). The structural requirements for D-AA8 analogues (antagonists) showed similarities with those of L-AA8 analogues (agonists). The latter three analogues, 29-31, were considerably more potent in vivo than their in vitro affinities would indicate, suggesting that these analogues may resist carboxypeptidase-like degradation. While partial agonist activity was not removed by D-AA8 substitution, [Sar1,D-Phe8]-AII-NH2 (31) displays lower partial agonist activity than [Sar1,Ile8]-AII. A receptor model is presented that highlights the difference between [L-AA8]-AII analogue agonist activity and [D-AA8]-AII analogue antagonist activity.