Abstract Model peptide substrates, e.g. glycyl-l-tyrosine, and inhibitors, e.g. β-(p-iodophenyl)propionate, are shown at 6 A resolution to bind to crystalline carboxypeptidase Aα in regions near the zinc atom. Although the question of bond formation of these added molecules to zinc must await studies at higher resolution, the present studies are not inconsistent with a direct role for the metal in enzymic reactions. Binding of glycyl-l-tyrosine to either native or acetylated crystals produces an increase in electron density in two adjacent regions (A and B) near the zinc. The main region (A) extends into the enzyme's pocket from above the zinc and is attributed to Gly-Tyr bound with its tyrosyl side chain projected into the pocket. Gly-Tyr bound to either apo- or copper-carboxypeptidase increases electron density only in Region A. Furthermore, there appears to be a structural change in the enzyme when substrates are bound to the native or modified enzyme.