Permeability enhancement of acidic lipid small unilamellar vesicles (dioleoylphosphatidylglycerol, DOPG; dipalmitoylphosphatidylglycerol, DPPG; bovine brain phosphatidylserine, PS) induced by magainins 1 and 2, basic antimicrobial peptides from Xenopus skin, was investigated at 30 degrees C based on leakage of calcein, an entrapped fluorescent marker. Both the peptide concentration and the lipid concentration dependencies of the leakage rate were analyzed to obtain the binding isotherms of the peptides to the membranes and the 'membrane-perturbing activities' of the membrane-bound peptides. For both peptides, the binding affinity was in the order DOPG greater than DPPG greater than PS, which coincided with the zeta potential order (-54, -39, and -9 mV, respectively). An increase in salt concentration of the medium reduced binding and leakage. Electrostatic interactions play a crucial role in the binding process. On the other hand, the membrane-perturbing activity is regulated by membrane fluidity: The fluid membranes (DOPG and PS) were leakier. A circular dichroism study suggested that at least 14 positively charged residues in the N-terminal regions can form amphiphilic helices which interact with the membranes. An even stronger binding of magainin 2 can be explained in terms of more positive charges in its N-terminal region. A tentative model for the magainin-lipid interactions is hypothesized.