Biodegradable pH-sensitive surfactants (BPS) are a unique family of easily metabolized compounds that demonstrate pH-dependent surface activity. These agents, in combination with other delivery systems, have demonstrated effects in enhancing transnucleic acid activity. The increased activity has been hypothesized to occur from a release of endosomal contents. Simply, the BPS delivery system containing nucleic acids enters the cell through an endocytotoic process. It encounters an acidic pH and becomes surface active leading to defects in the endosomal membrane. In the current study, an in vitro model membrane was used to better understand the liposome defect mechanisms that BPS elicit. Using this system, it is shown that BPS can induce both liposome fusion and rupture depending upon the pH and mole ratio of BPS to membrane lipids. Futhermore, liposome fusion induced by BPS was dependent on the total numbers of liposome particles while rupture was independent of interacting liposome particles. The generated data indicate that BPS agents act differently from other typical surface active agents and fuosgenic compounds. Instead of facilitating membrane fusion through the hexagonal II phase, BPS appeared to contribute and participate in the membrane fusion at different stages.