Thirteen different polypeptide subunits, each in one copy, five phosphatidyl ethanolamines and three phosphatidyl glycerols, two hemes A, three Cu ions, one Mg ion, and one Zn ion are detectable in the crystal structure of bovine heart cytochrome c oxidase in the fully oxidized form at 2.8 A resolution. A propionate of hems a, a peptide unit (-CO-NH-), and an imidazole bound to CuA are hydrogen-bonded sequentially, giving a facile electron transfer path from CUA to heme a. The O2 binding and reduction site, heme a3, is 4.7 A apart from CuB. Two possible proton transfer paths from the matrix side to the cytosolic side are located in subunit I, including hydrogen bonds and internal cavities likely to contain randomly oriented water molecules. Neither path includes the O2 reduction site. The O2 reduction site has a proton transfer path from the matrix side possibly for protons for producing water. The coordination geometry of CuB and the location of Tyr244 in subunit I at the end of the scalar proton path suggests a hydroperoxo species as the two electron reduced intermediate in the O2 reduction process.