We have combined two-dimensional infrared (2D IR) spectroscopy and isotope substitutions to reveal the vibrational couplings between a pair of amide-I and -II modes that are several residues away but directly connected through a hydrogen bond in a helical peptide. This strategy is demonstrated on a 3(10)-helical hexapeptide, Z-Aib-L-Leu-(Aib)(2)-Gly-Aib-OtBu, and its C-13=O-18-Leu monolabeled and C-13=O-18-Leu/N-15-Gly bis-labeled isotopomers in CDCl3. The isotope-dependent amide-I/II cross peaks clearly show that the second and fourth peptide linkages are vibrationally coupled as they are in proximity, forming a 3(10)-helical turn. The experimental spectra are compared to simulations based on a vibrational exciton Hamiltonian model that fully takes into account the amide-I and -II modes. The amide-II local mode frequency is evaluated by a new model based on the effects of hydrogen-bond geometry and sites. Ab initio nearest-neighbor Coupling maps of the amide-I/I, -I/II, -II/I and -II/II modes are generated by isotopically isolating the local modes of N-acetyl-glycine N'-methylamide (AcGlyNHMe). Longer range couplings are modeled by transition charge interactions. The effects of the capping groups are incorporated and isotope effects are analyzed based oil ab initio calculations of six model compounds. The main features of the 2D IR spectra are reproduced by this modeling. The conformational sensitivity of the isotope-dependent amide-I/II cross peaks is discussed in comparison with the calculated spectra for a semiextended structure. Our experimental and theoretical Study demonstrates that the combination of 2D IR and C-13=O-18/N-15 labeling is a useful structural method for detecting helical turn formation with residue-level specificity.