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 (CcO(rest). CN) gave intense isotope sensitive bands at 478, 473, 473, and 468 cm(-1) for the (CN-)-C-12-N-14, (CN-)-C-13-N-14, (CN-)-C-12-N-15, and (CN-)-C-13-N-15 adducts. respectively, which were distinctly higher than those for cyanometHb (HbCN) and cyanometMb (MbCN), presumably due to interactions with the Cu-B 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 (nu(Fe-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 N-15 isotopes compared with C-13 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 (delta(FeCN)) is present around similar to 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 (nu(CN)) mode of CN--bound heme proteins was observed in Raman spectra for the first time.