Among Various alcohols, those substituted with fluorine, such as 2,2,2-trifluoroethanol (TFE) or 3,3,3,3',3',3'-hexafluoro-2-propanol (HFIP), have a marked potential to induce the formation of alpha-helical structures in peptides and to denature the native structures of proteins. However, the mechanism by which these alcohols exert their effects is unknown. Melittin, a bee venom peptide, is unfolded in the absence of alcohol, but is transformed to an alpha-helical structure upon addition of alcohols. On the other hand, addition of alcohols to beta-lactoglobulin, a predominantly beta-sheet protein, denatures the molecule and transforms it to an alpha-helical structure. We examined the role of several factors in these alcohol-induced transitions, i.e., relative dielectric constant, strength of hydrogen bond estimated by the pH titration of salicylic acid, and clustering of alcohol molecules measured by solution X-ray scattering. Although relative dielectric constant and hydrogen bond strength were confirmed to be important, they did not explain the marked effects of TFE and HFIP. X-ray scattering detected clusters of TFE or HFIP molecules in alcohol/water mixtures with a maximum at around 30% (v/v) of each alcohol. When the conformational transitions induced by TFE and HFIP were plotted against the extent of cluster formation by the corresponding alcohol/water mixtures, the TFE and HFIP-induced transition curves agreed with each other for both melittin and beta-lactoglobulin, This suggests that clustering of alcohol molecules is an important factor that enhances the effects of alcohols on proteins and peptides.