A method for evaluating secondary and tertiary structure of a polypeptide in solution. The amide hydrogens of the polypeptide backbone slowly exchange with water hydrogens, unless they are non-covalently bonded to neighbouring basic groups, such as amide oxygen atoms (as in an a-helix) or carboxylates groups. If the peptide is first equilibrated with D₂O to replace exchangeable hydrogens with deuterium, and then placed in H₂O, the rate of appearance of deuterium in the bulk water phase will be determined by the chemistry of the sites to which deuterium is bound (amine hydrogens will very rapidly exchange) and availability of the exchangeable sites, as determined by the secondary or tertiary structure.