Three hydrophobic derivatives of GHK peptide containing either N-terminal hexanoyl, decanoyl or myristoyl acyl moieties were synthesized. The binding of these peptidolipids to phospholipid bilayers as well as their hemolytic activity were determined. Moreover, the influence of these peptidolipids on several physicochemical properties of liposomes was studied. Binding experiments indicate a high affinity of these peptidolipids for lipids ordered in liposomes. Nevertheless, this interaction does not promote the release of entrapped carboxyfluorescein. Experiments carried out by the asymmetric membrane method (NBD-PE/dithionite) and quenching studies (PC-pyrene/KI) indicate that this association has a protective effect suggesting that the hydrophobic moiety inserts in the external part of the bilayer and the peptide chain remains protruding from the surface hindering the entrance or the approach of reactants to it. The microviscosity of DPPC bilayers determined using TMA-DPH as fluorescent marker was not affected by the presence of peptidolipids. Besides, results indicate that myristoyl-GHK produces total hemolysis at 2.5x10(-4)M but decanoyl and hexanoyl derivatives at 5x10(-4)M induce only 10% of hemolysis.