Measurements of proton transverse relaxation rates, R-2 and R-1 rho, have not been commonly performed for proteins because cross correlations among the numerous H-1-H-1 dipolar interactions complicate analysis of the data. In addition, these interactions make large contributions to the relaxation of the amide protons, making it difficult to detect if an exchange of chemical shifts also makes a contribution, R-ex, to relaxation. To overcome these problems, we have investigated proton relaxation of a perdeuterated protein, HIV-1 protease, bound to a small protonated inhibitor DMP323. Perdeuteration significantly reduces the contributions of H-1-H-1 dipolar interactions to the relaxation of the amide protons. The ROESY R-1 rho experiment further reduces the overall relaxation rate as compared with the usual R-1 rho experiment because the protons relax as unlike spins, with rate R-1 rho.unlike. in the former experiment but as like spins, with rate R-1 rho, in the latter. These reductions of the proton transverse-relaxation rate facilitated the detection of R-ex contributions at several sites in the protein (1) from the B-1-field dependence of R-1 rho,R-unlike and (2) by comparing R-1 rho,R-unlike values with relaxation rates, R-2, obtained from Carr-Purcell-Meiboom-Gill (CPMG) and Hahn-echo experiments. The significant reduction of the proton spin-flip rate in the perdeuterated protein enabled measurement of N-15 R-2 values using the CPMG method and the same large duration between 180 degrees pulses as used in the H-1 CPMG experiments. Hence, relaxation data of both nuclei were utilized to obtain complementary information about sites experiencing exchange of chemical shifts in the protein.