Poly(2-ethylacrylic acid) [PEAA] was shown to induce fusion of phosphatidylcholine bilayer membranes under mildly acidic conditions. The pH-dependent destabilization and fusion of extruded large unilamellar vesicles (LUVs) by PEAA was characterized by optical density measurements, transmission electron microscopy, and lipid-mixing and contents-release assays. Reduction of either the chain length or the polymer concentration caused the fusion and contents-release events to shift to lower pH values. Release of entrapped calcein was observed at pH values approximately 1 unit higher than those found to cause membrane fusion. Decreased levels of fusion were observed when the concentration of PEAA was lower than that of the lipid; however, quantitative release of encapsulated calcein could be effected at very low polymer concentrations (similar to 3% w/w PEAA./lipid).