The problem of assigning lines in the NMR spectra of peptides to sequence specific am ino acids is an important one whose general solution involves finding some kind of connectivity between spectral components associated with adjacent residues (see F ig. 1). To this end, a variety of schemes involving one-dimensional and, more recently, two-dimensional techniques have been proposed (I-13) none of which are free of lim itations. In principle, the most straightforward strategy is to look for cross relaxation (NOES) between the proton on the (Y carbon of the ith residue and the am ide proton of the next residue at i + 1 (Z-3). For success, this experiment must generally be done in HZ0 or aprotic solvents in order to m inimize the effects of chemical exchange between the am ide and the solvent protons. In aqueous solutions at a physiologic pH, however, the exchange reaction may be so rapid that the identities of individual NH resonances are obliterated by exchange broadening. This is frequently the case for linear peptides as well as polypeptide segments in proteins that have poorly defined secondary structure and are exposed to the solvent. Indeed the success of any NMR method that involves correlations with am ide protons (1-3, 7-11, 13) will be constrained by the specifics of the NH-solvent exchange kinetics. An alternative method that avoids the problems with exchange is one in which connectivity between the a! protons of adjacent am ino acids is established through their respective twoand three-bond scalar couplings to the 13C’ of the intervening carbonyl group (5, 6, 12, 13). Heteronuclear correlation experiments such as these, involving mu ltibond or long-range coherence transfer, suffer, however, from poor sensitivity, especially if done using 13C detection (5-9, II, 14). In part this is a consequence of the low gyromagnetic ratio of carbon13 as well as its scarcity in nature. O ther contributing factors include (1) the inefficiency of coherence transfer through weak, mu ltibond couplings, ‘2,3)J(HC) that are the same order of magn itude as the natural linewidths; and (2) losses in signal due to interference arising from homonuclear couplings (passive spin effects (14, 15)). As amp ly demonstrated (9, 16-18) the sensitivity of the heteronuclear correlation experiment can be enhanced significantly by using proton detection, particularly