The permeability effects induced by single-chained and double-chained poly(ethylene glycol)-surfactants were investigated by measuring the leakage of the fluorescent dye 5(6)-carboxy fluorescein from EPC liposomes. The standard incorporated amount of the surfactants was 5 mol%. Depending on the size of the poly(ethylene glycol) chain and especially on the type of linkage between the polymer and the hydrophobic moiety different leakage profiles were obtained. The presence of a long PEG-polymer resulted in a slower leakage compared with a short analogue. More importantly, the linkage identity was decisive for whether an overall reduction or increase in permeability was obtained. When the hydrocarbon chains were attached to the PEG chain via an ether or an ester the leakage increased compared to pure EPC liposomes. In contrast, if the link was an amide, the leakage was significantly reduced. This effect is assumed to originate from headgroup–headgroup interactions, and most probably hydrogen bonding, between amide and phosphate groups of the PEG-surfactant and the EPC, respectively