Waterprotein interactions play a central role in protein structure, dynamics, and function. These interactions, traditionally, have been studied using nuclear magnetic resonance (NMR) by measuring chemical exchange and nuclear Overhauser effect (NOE). Polarization transferred from hyperpolarized water can result in substantial transient signal enhancements of protein resonances due to these processes. Here, we use dissolution dynamic nuclear polarization and flow-NMR for measuring the pH dependence of transferred signals to the protein trypsin. A maximum enhancement of 20 is visible in the amide proton region of the spectrum at pH 6.0, and of 47 at pH 7.5. The aliphatic region is enhanced up to 2.3 times at pH 6.0 and up to 2.5 times at pH 7.5. The time dependence of these observed signals can be modeled quantitatively using rate equations incorporating chemical exchange to amide sites and, optionally, intramolecular NOE to aliphatic protons. On the basis of these two- and three-site models, average exchange (k(ex)) and cross-relaxation rates (sigma) obtained were k(ex) = 12 s(1), s = -0.33 s(1) for pH 7.5 and k(ex) = 1.8 s(1), s = -0.72 s(1) for pH 6.0 at a temperature of 304 K. These values were validated using conventional EXSY and NOESY measurements. In general, a rapid measurement of exchange and cross-relaxation rates may be of interest for the study of structural changes of the protein occurring on the same time scale. Besides proteinwater interactions, interactions with cosolvent or solutes can further be investigated using the same methods.