Dark state exchange saturation transfer (DEST) and lifetime line-broadening (Delta R-2, the difference in the measured transverse relaxation rates for the observable species in the presence and absence of exchange with a species characterized by very large intrinsic transverse relaxation rates) have proven to be powerful NMR tools for studying exchange phenomena between a NMR visible species and a high-molecular weight, "dark", NMR invisible state. However, in the exchange regime, where the transverse spin relaxation rates in the bound state (R-2(bound)) are smaller than the strength of the DEST saturation radio frequency field, typically corresponding to systems below similar to 6 MDa, the combination of DEST and Delta R-2 data, while sufficient to define the apparent association rate constant, cannot unambiguously determine the population of the bound state p(B) and R-2(bound) values independently. We show that the latter exchange and relaxation parameters can be decorrelated by the measurement of the maximal value of the contribution of the fast-relaxing magnetization component to the total NMR signal, C-fast(max), an observable that is directly proportional to p(B). When integrated into the analysis of DEST/Delta R-2 data, C-fast(max) provides an indispensable source of information for quantitative studies of exchange involving high-molecular-weight dark states. We demonstrate the utility of this approach by investigating the binding kinetics of two huntingtin exon-l-derived peptides to small unilamellar lipid vesicles (SUV), similar to 31 nm in diameter and 4.3 MDa in molecular weight. The interaction of the N-terminal amphiphilic domain of huntingtin exon-1 with membrane surfaces promotes polyglutamine-mediated aggregation and, as such, is thought to play a role in the etiology of Huntington's disease, an autosomal dominant fatal neurodegenerative condition. The first peptide comprises the 16-residue N-terminal amphiphilic domain (htt(NT)) alone, while the second contains an additional seven residue polyglutamine tract at the C-terminus (htt(NT)Q(7)). At a peptide-to-lipid molar ratio of 1:4, the population of peptide bound to the SUV surface is substantial, similar to 7-8%, while exchange between the free and SUV-bound peptide is slow on the relaxation time-scale (k(ex) similar to 200 s(-1)). The last two C-terminal residues of htt(NT) and the last 9 of htt(NT)Q(7) remain flexible in the SUV-bound form due to transient detachment from the lipid surface that occurs on a time scale several-fold faster than binding.