The CN-isotope-sensitive resonance Raman (RR) bands were investigated for CN- adducts of hemoglobin (Hb), myoglobin (Mb), and cytochrome c oxidase (CcO). All proteins gave multiple CN-isotope-sensitive bands around 450−480 and 340−440 cm-1. The CN--bound resting CcO (CcOrest·CN) gave intense isotope-sensitive bands at 478, 473, 473, and 468 cm-1 for the 12C14N-, 13C14N-, 12C15N-, and 13C15N- adducts, respectively, which were distinctly higher than those for cyanometHb (HbCN) and cyanometMb (MbCN), presumably due to interactions with the CuB ion present at the binuclear site. The monotonous feature of the frequency changes upon the increase of a total mass of CN suggests that these bands arise from the Fe−CN stretching mode (νFe-CN). Besides this main band, several weak CN-isotope-sensitive bands were observed below 440 cm-1 for all three proteins, but the pattern of the isotope-difference spectra was specific to each protein. These low-frequency difference peaks were significantly weaker in intensity for 15N isotopes compared with 13C isotopes in common. The band-fitting calculations indicated that the Raman intensities of several porphyrin vibrations were altered by CN isotopes without changing their frequencies, suggesting that the Fe−C−N bending mode (δFeCN) is present around ∼380 cm-1 and this mode is coupled with more than two porphyrin vibrations which differ among Hb, Mb, and CcO. The C−N stretching (νCN) mode of CN--bound heme proteins was observed in Raman spectra for the first time.