We have examined the effect of trifluoroethanol (TFE) on the solution behaviour of three amphipathic peptides. One of the peptides, containing three heptad repeat units (Ac-YS-(AKEAAKE)3GAR-NH2), remained monomeric under conditions where TFE induced a two-state transition from a random coil to an alpha-helix. In contrast, the TFE-induced alpha-helical formation of two peptides derived from human apolipoproteins C-II and E was accompanied by the formation of discrete dimers and trimers, respectively. The apolipoprotein C-II peptide further aggregated to form beta-sheet at higher concentrations of TFE (50% v/v). The results suggest a class of peptides capable of discrete self-association in the presence of cosolvents which favour intramolecular hydrogen bonding.