We used the molecular recognition hypothesis, that peptide ligands and their receptor binding sites are encoded by complementary nucleotide sequences , to purify a angiotensin II (Ang II) bindi g protein. The complementary peptide IIA (Lys-Gly-ValAsp- Val-Tyr-Ala-Val) specified by the RNA sequence complementary to the messenger (m)RNA sequence for rat Ang II was synthesized, purified and used to raise polyclonal antibodies. Complementary peptide IIA specifically inhibited the binding of 1251_Ang II to receptors on rat adrenal membranes, and anti-IIA immunoglobulin G (lgG) specifically inhibited the binding of 1251_Ang II to rat adrenal Ang II receptors and Ang II-dependent aldosterone secretion by cultured rat adrenal cells, suggesting that the antibody recognizes the Ang II receptor. Anti-IIA IgG was used for immuno-affinity purification, from a rat adrenal membrane preparation of an Ang II binding protein with a molecular weight of 66 000 ± 2000 that bound 1251_Ang II specifically. This is the first report of purification of an Ang II receptor binding protein which retains its capacity to specifically bind 1251_Ang II. © Gower Academic Journals Ltd.