It has Iona been suggested that existence of partially folded intermediates may be essential for proteins to fold in a biologically meaningful time scale. Although partially folded intermediates have been commonly observed in larger proteins, they are generally not detectable in the kinetic folding of smaller proteins (similar to100 amino acids or less). Recent native-state hydrogen exchange studies suggest that partially folded intermediates may exist behind the rate-limiting transition state in small proteins and evade detection by conventional kinetic methods. Published by Elsevier Science (USA).