Cytochrome c oxidase (COX) from bovine heart contains the EPR-detectable mixed valent [CuA(1.5) CuA(1.5)], S = 1/2 center and the EPR non-detectable CuB site. The addition of four equivalents of Cu2+ to COX did not aggregate the enzyme or affect its activity. EPR parameters for these sites are g = 2.22 and A = 195 G. Nitrogen superhyperfine structure was observed in the g region. These parameters are very close to those for Cu2+, which is bound to the 2 -histidine of the chain N-terminus in tetramer hemoglobin. By analogy, tentative assignments of these binding sites are proposed to be at the N-terminus of subunits of COX, for example, subunit IV where the sequence is A-H-G-S . Nitrogen donor atoms from the `-amino group of the amino terminal residue, the imidazole group of histidine, and the peptide nitrogens comprise the binding site. To our knowledge, a type 2 signal with these parameters has only been found at the N-terminus for which histidine is either the 2nd or 3rd residue. At the N-terminus, the flexibility of the protein chain is not yet hindered by `-helix or -sheet constraints.