Angiotension II is the effector molecule of the renin-angiotensin system. Therefore, agents directed at the receptor that mediates its actions are likely to represent the most physiologically specific inhibitors of the system. We suggest here an approach to such drugs based on an operational analogy between peptidases and peptide hormone receptors and on the development of inhibitors of angiotensin-converting enzyme. The rationale that led to captopril, enalapril, and related inhibitors of this peptidase required identification of its cognitive and functional properties, i.e., what amino acid sequences it preferentially recognizes and its Zn2+ -dependent dipeptidyl carboxypeptidase activity. Purification of the enzyme was necessary to obtain this information. We speculate that this type of information may be equally useful for developing a receptor antagonist. As progress toward this objective, we describe briefly purification of rabbit hepatic angiotensin II receptor using chemical and immunoaffinity ligands. We hope to determine the cognitive and functional properties of this purified protein, i.e., what residues it preferentially recognizes in defined peptides and the molecular mechanism by which binding of ligand is transduced into a cellular response.