Synopsis The liposome-surfactant interaction has been studied in this paper through the disrupting effect caused by surfactant molecules on large unilamellar vesicles prepared by reverse-phase evaporation. This process leads, in the end, to the rupture of such structures and to the solubilization of the phospholipidic components, via mixed surfactant-phospholipid micelle formation. This phenomenon is described by a three-stage model and characterized by two parameters: the highest surfactant/phospholipid ratio that can exist in a vesicle (R(e sat)) and the lowest surfactant/phospholipid ratio required to keep the lipid and surfactant in the form of mixed micelles (R(e sat)). These parameters have been determined by spectrophotometry and (31)P NMR spectroscopy, obtaining results in a good agreement with both techniques. The surfactants tested have been: sodium dodecyl sulfate (SDS), sodium laurylether sulfate (SLES), N-hexadecyl-trimethylammonium bromide (HTAB), octylphenol series (8-20 EO) and alkylbetaines(C-10, C-12 and C-14). Different R(e sat) and R(e sol) values have been obtained for each of the surfactants. This has permitted a study of the solubilizing capacity versus the phospholipidic bilayer of the different surfactants as a function of their structure.