This study investigates the screening effect of poly(ethylene glycol)-phospholipids (PE-PEG) on the interaction of avidin with PEGylated liposomes containing surface-bound biotin ligands. The influence of grafting density and lipopolymer chain length is examined. A simple fluorescence assay involving a receptor-mediated fluorescence increase of BODIPY-labeled avidin upon binding to biotinylated lipids is employed to study the screening effect of submicellar concentrations of 1,2-dipalmitoyl-sn-glycero-3-phosphatidylethanolamine-N-[poly(ethylene glycol)-2000] (PE-PEG²⁰⁰⁰) and 1,2-dipalmitoyl-sn-glycero-3-phosphatidylethanolamine-N-[poly(ethylene glycol)-5000] (PE-PEG⁵⁰⁰⁰) incorporated into 1,2-dipalmitoyl-sn-glycero-3-phosphatidylcholine (DPPC) liposomes. The results show that incorporation of lipopolymers into DPPC lipid bilayers reduces binding of avidin to the biotinylated liposomes, and it is found that the screening effect of PE-PEG⁵⁰⁰⁰ is stronger than that for PE-PEG²⁰⁰⁰. Thus, the results reveal that both the grafting density and the polymer length of the PE-PEG lipopolymers are of importance for the ability of water-soluble macromolecules to reach the surface of PEG liposomes. Furthermore, it is found that none of the lipopolymers completely prevents avidin from reaching the surface-bound biotin ligands.