AbstractIn this study, the octapeptide hormone, angiotensin II (H‐Asp1‐Arg2‐Val3‐Tyr4‐Ile5‐His6‐Pro7‐Phe8‐OH; AII), and various AII homologues and analogues were employed as an antigen system to investigate the binding specificities of guinea pig antibodies. Using small, precisely defined peptides facilitates the comparison of the antigen‐binding repertoire of antibodies with the antigen specificities of T cells since unconju‐gated AII elicits both cellular and humoral immune responses. The T cell proliferative response has previously been shown to be exquisitely specific and under Ir gene control. In contrast, antibody binding, as reported here, was decidedly less specific and independent or the Ir gene control reported for the T cell proliferative response. Antisera from individual strain 2 or 13 guinea pigs immunized with either AII or [Val5]‐AII contained IgG antibodies that were highly restricted by isoelectric focusing but capable of binding either antigen with nearly equal efficiency, as determined by competitive inhibition studies in radioimmunoassays. The fine specificity of antibody binding was examined through the use of a series of AII homologues and analogues for competitive inhibition. The important residues for peptide‐antibody binding were Phe8, His6, Tyr4, and Asp1, since analogues with residue substitutions at these sites were much less efficient inhibitors. These results are discussed with respect to the differences in recognition of peptide antigenic dete