The interactions of two amphiphilic and cationic, nine-residue beta-peptides with liposomal membranes were studied. These beta-peptides are shown to form 14-helices in the presence of bilayers. Membrane binding and membrane permeabilization occur preferentially in the presence of anionic lipids. The beta-peptides have the ability to cause tranbilayer diffusion of phospholipids, form pores, and promote lipid mixing between liposomes. These beta-peptides have previously been shown to display antimicrobial activity comparable to that of a longer beta-peptide, beta-17, which adopts a different type of helical conformation (12-helix), and to the 23 amino acid (Ala(8,13,18))-magainin-II-amide, which adopts an alpha-helical conformation. In addition, these 14-helical beta-peptides show relatively low hemolytic activity. The biological potency and microbial specificity of the 14-helical beta-peptides, despite their relatively short length, suggests that 14-helices can be particularly disruptive to microbial membranes.