The interactions of ovalbumin (OA) with large unilamellar vesicles (LUV) of phosphatidylserine (PS) and PS/phosphatidlethanolamine (PE) were studied. It was observed that OA induces aggregation, destabilization, and fusion of these LUV containing a phospholipid at low pH levels. The fusion of LUV by OA was monitored the intermixing of internal aqueous contents of vesicles the resonance energy transfer assay which follows the mixing of membrane components and thin-sectioning electron microscopy. A pH profile of fusion was found to be similar to the pH-dependent binding of OA to the same phospholipid vesicles. Proteoltic digestion and hydrophobic labeling with dansl chloride and photoreactive phosphatidylcholine (PC) of OA-vesicle complex showed that a segment of OA with a molecular weight of approximately 2,500 penetrates the bilayer. The amino acid composition of this segment indicated that it is the 291-322 fragment and not the putative signal sequence. OA inflenced the spin labels (12-PGSL) deep inside the bilaer of PS vesicles while only one (5-PGSL) near the surface was affected for the case of PS/PE (1:1) vesicles.