The interactions between sterically stabilized (EPC/PEG-lipid) liposomes and the nonionic surfactants octyl glucoside (OG) and octa(ethylene glycol) n-dodecyl monoether (C12E8) have been studied. Cryogenic transmission electron microscopy revealed that poly(ethylene glycol)-lipids (PEG lipids) affected the OG-mediated solubilization of the liposomes. Long-lived small bilayer disks were observed at OG concentrations saturating the bilayers. In addition, the macroscopic phase separation observed in EPC/OG systems, at OG concentrations such that the bilayers were close to being solubilized, was entirely inhibited by the inclusion of PEG-lipids in the membrane. OG was more efficient in destabilizing sterically stabilized liposomes than conventional ones, whereas for C12E8 the effective molar ratio of surfactant to lipid at bilayer saturation was essentially the same for both types of liposomes. Furthermore, the results reported illuminate the effect of PEG-lipids on, and the mechanism of surfactant-induced growth of small unilamellar vesicles.