Analogues of [Sar1]angiotensin II, Sarilesin (type I antagonist), and Sarmesin (type II antagonist) with L-azetidine-2-carboxylic acid (Aze) and L-pipecolic acid (Pip) at position 7 have been prepared by the solid-phase method, purified by reverse-phase HPLC, and bioassayed in the rat uterus. Analogues of the superagonist [Sar1]ANGII with Aze or Pip at position 7 and sarcosine (Sar) or aminoisobutyric acid (Aib) at position 1 had high intrinsic activity in the rat isolated uterus assay (34-184%). Analogues of Sarilesin ([Sar1,Ile8]ANGII) with Aze or Pip at position 7 and Sar or Aib at position 1 retained high antagonist activity (pA2 = 7.1-8.3). Analogues of Sarmesin ([Sar1,Tyr-(OMe)4]ANGII) with Aze and Pip at position 7 had pA2 values of 7.4 and 6.5, respectively. [Aze7]-ANGII and [Pip7]ANGII had low activities (12% and 1%, respectively), and deletion of Sar at position 1 of Sarmesin analogues abolished binding (or affinity) as judged from pA2 values. Nuclear Overhauser effect (NOE) spectroscopy studies of [Sar1,Aze7]ANGII in DMSO-d6 have indicated a clustering of the three aromatic rings (Tyr, His, Phe) and proximity of Sar C alpha and Arg C delta protons to the Tyr/Phe ring protons. These data emphasize that replacement of Pro with the lower and higher homologs Aze and Pip does not greatly alter the structural requirements necessary for expression of agonist or antagonist activity, when sarcosine occupies position 1, but not when Asp occupies position 1, suggesting that there is an intimate relationship between the N-terminal and penultimate residues of the molecule in the biologically active conformation of the molecule.