Results of a study of internal electron transfer in bovine heart cytochrome c oxidase with the method of tunneling currents are presented. Electronic structure of the protein complex is treated at the semiempirical extended Huckel level. Two distinct pathways connecting Cu-A and heme a are found, one of them is similar to proposed earlier in the literature, the other is new. The pathway connecting heme a and heme a(3) is also identified. This pathway differs from those proposed before. The calculated reaction rates between Cu-A and Fe-a and between Fe-a and Fe-a3 are in reasonable agreement with experimental data. The tunneling matrix element for electron transfer from Cu-A to the binuclear site is found to be very small, which is consistent with experimental evidence of the absence of this reaction. With the assumption that evolution places constraints on functionally important amino acids, we suggest that amino acids implicated in the electron-transfer pathways will show a high degree of conservation in different organisms. Sequence analysis performed on subunit I and II revealed that this is indeed the case: amino acids of the identified tunneling pathways showed very little evolutionary variability.