An approach is presented that allows a detailed, quantitative characterization of conformational exchange processes in proteins on the mus-ms time scale. The approach relies on a combined analysis of NMR relaxation rates and chemical shift changes and requires that the chemical shift of the exchanging species can be determined independently of the relaxation rates. The applicability of the approach is demonstrated by a detailed analysis of the conformational exchange processes previously observed in the reduced form of the blue copper protein, plastocyanin from the cyanobacteria Anabaena variabilis (A.v. PCu) (Ma, L.; Hass, M. A. S.; Vierick, N.; Kristensen, S. M.; Ulstrup, J.; Led, J. J. Biochemistry 2003, 42, 320-330). The R-1 and R-2 relaxation rates of the backbone N-15 nuclei were measured at a series of pH and temperatures on an 15N labeled sample of A.v. PCu, and the 15 N chemical shifts were obtained from a series of HSQC spectra recorded in the pH range from 4 to 8. From the R-1 and R-2 relaxation rates, the contribution, R-ex, to the transverse relaxation caused by the exchanges between the different allo-states of the protein were determined. Specifically, it is demonstrated that accurate R-ex terms can be obtained from the R-1 and R-2 rates alone in the case of relatively rigid proteins with a small rotational anisotropy. The R-ex terms belonging to the same exchange process were identified on the basis of their pH dependences. Subsequently the identifications were confirmed quantitatively by the correlation between the R-ex terms and the corresponding chemical shift differences of the exchanging species. By this approach, the R-ex terms of N-15 nuclei belonging to contiguous regions in the protein could be assigned to the same exchange process. Furthermore, the analysis of the exchange terms shows that the observed mus-ms dynamics in A. v. PCu are caused primarily by the protonation/deprotonation of two histidine residues, His92 and His61, His92 being ligated to the Cu(l) ion. Also the exchange rate of the protonation/deprotonation process of His92 and its pH and temperature dependences were determined, revealing a reaction pathway that is more complex than a simple specific-acid/base catalysis. Finally, the approach allows a differentiation between two-site and multiple-site exchange processes, thus revealing that the protonation/deprotonation of His61 is at least a three-site exchange process. Overall, the approach makes it feasible to obtain exchange rates that are sufficiently accurate and versatile for studies of the kinetics and the mechanisms of local protein dynamics on the sub-millisecond time scale.