The mechanisms governing the interaction of equimolecular mixtures of nonylphenol polyethoxylated with 10 mol of ethylene oxide (NP(EO)(10)) and sodium dodecyl sulfate (SDS) with phosphatidylcholine (PC) Liposomes were investigated. Permeability alterations were detected as a change in 5(6)-carboxyfluorescein (CF) released from the interior of vesicles and bilayer solubilization was detected as a decrease in the static light scattered by liposome suspensions. At the subsolubilizing level, a maximum bilayer/water partitioning of surfactant mixture was reached at 30-50% CF release, which correlated with the increased presence of SDS in the bilayers. However, transition stages between 60% CF release and 100% light scattering corresponded to the increased presence of NP(EO)(10) in these structures. The surfactant mixture showed throughout the interaction a much higher affinity with bilayers and a higher ability to saturate and solubilize these structures than that reported for the anionic component. A direct dependence was established in the initial interaction steps (effective molar ratio of surfactant to phospholipid in bilayers (R(e)) lower than 0.190) between the growth of vesicle fluidity and the maximum bilayer/water partitioning of the surfactant mixture (K). These parameters also depended on the surfactant saturation of the outer vesicle leaflet. A linear dependence was also established during solubilization between the decrease in both the surfactant-PC aggregate size and the scattered light of the system and the composition of these aggregates (R(e)). The fact that the free surfactant concentration at subsolubilizing and solubilizing levels was respectively lower than and similar to the critical micelle concentration (cmc) of the surfactant mixture indicates that permeability alterations and solubilization were determined respectively by the action of the surfactant monomer and by the formation of mixed micelles. This finding supports the generally admitted assumption, for single surfactants, that the concentration of free surfactant must reach the cmc for solubilization to occur and highlights the influence of the negative synergism of this surfactant mixture on the free surfactant concentration needed to saturate or solubilize liposomes.