The effect of poly(ethylene glycol)-phospholipid (PE-PEG) lipopolymers on phospholipase A₂ (PLA₂) hydrolysis of liposomes composed of stearoyl-oleoylphosphatidylcholine (SOPC) was investigated. The PLA₂ lag-time, which is inversely related to the enzymatic activity, was determined by fluorescence, and the zeta-potentials of the liposomes were measured as a function of PE-PEG lipopolymer concentration. A significant decrease in the lag-time, and hence an increase in enzymatic activity, was observed with increasing amounts of the negatively charged PE-PEG lipopolymers incorporated into the SOPC liposomes. The enhancement of the PLA₂ enzymatic activity might involve a stronger PLA₂ binding affinity towards the negatively charged and polymer covered PEG liposomes.