The interaction of mixtures of sodium dodecyl sulfate (SDS) and oxyethylenated nonylphenol (30 mol of ethylene oxide) [NP(EO) 30 ] with phosphatidylcholine liposomes was investigated. Permeability alterations were detected as a change in 5(6)-carboxyfluorescein (CF) released from the interior of vesicles, and bilayer solubilization was measured as a decrease in the static light scattered by liposome suspensions. Three parameters were described as the effective surfactant/lipid molar ratios (Re) at which the surfactant system: (i) resulted in 50% CF release (Re 50%CF ); (ii) saturated the liposomes (Re SAT ); (iii) led to complete solubilization of these structures (Re SOL ). The corresponding surfactant partition coefficients (K 50%CF , K SAT , and K SOL ) were determined from these parameters. The free surfactant concentrations S W were lower than the mixed surfactant critical micellar concentration at subsolubilizing levels, whereas they remained similar to these values during saturation and solubilization of bilayers. Although the Re values increased linearly as the mole fraction of the SDS rose (X SDS ), the K parameters showed maximum values at X SDS 0.6 for K 50%CF and approximately at X SDS 0.2 for K SAT and K SOL , respectively. Thus, the lower the surfactant contribution in the surfactant/lipid system, the higher the X SDS at which the maximum bilayer/water partitioning of added mixed surfactant systems occurred. As a consequence, the influence of SDS in this partition appears to be more significant at the sublytic level (monomeric effect), whereas the influence of NP(EO) 30 seems to be greater during saturation and solubilization of liposomes via formation of mixed micelles. JAOCS 74, 9-17 (1997). KEY WORDS: Carboxyfluorescein release, partition coefficients, permeability alterations and bilayer solubilization, phosphatidylcholine liposomes, sodium dodecyl sulfate/nonylphenol oxyethylenated [NP(EO) 30 ] mixtures, static light-scattering, surfactant/phospholipid molar ratios.The interaction of sodium dodecyl sulfate (SDS) with skin induces structural changes in the epidermal surfaces (1-3) and in the stratum corneum transcutaneous permeability barrier (4,5). Mixtures of this anionic surfactant with oxyethylenated nonylphenols of different oxyethylenation levels in aqueous solution show negative deviation from ideal solution behavior (6-10). These mixtures also exhibit changes in the surface properties that improve the wetting ability of water on hydrophobic surfaces (11,12) and the salinity tolerance with regard to that of the anionic component (13). The change in the physico-chemical properties of mixed micelles and their additional stability arises from the charge separation of the ionic head groups, which affects the mean aggregation numbers of these micelles (8,14).A number of investigations have been devoted to the understanding of the principles that govern the interaction of SDS with simplified membrane models, such as phospholipid or stratum corneum lipid bilayers, when this surfactant interact...