Perfluorocarbon (PFC) nanoparticles can serve as a very specific site-targeted contrast and therapeutic agent after binding to specific cellular biomarkers. Ultrasound has been used in conjunction with microbubbles to enhance the delivery of drugs and genes into the cell, mainly through the process of cavitation. We have demonstrated earlier that ultrasound at 2 MHz (1.9 MI) for 5 min can enhance the interaction of nanoparticles with targeted cells. In this study, we sought to establish that nanoparticles used in conjunction with ultrasound do not act as "cavitation" foci. Cell-culture inserts were seeded with human umbilical vein endothelial cells (HUVECs) and exposed to ultrasound in the presence of either Definity® or PFC nanoparticles. Definity® in conjunction with continuous wave ultrasound (2.25 MHz for 1 and 5 minutes) increased the permeability of monolayer by four to six times above the normal, decreased trans-endothelial electrical resistance (a sign of reduced membrane integrity), and decreased cell viability by ∼50%. Histological evaluation demonstrated extensive disruptions of cell monolayers. Nanoparticles (both non-targeted and targeted) elicited no changes in the measured parameters under similar insonification conditions. Sonically enhanced delivery of drugs from liquid perfluorocarbon nanoparticles to targeted cells does not involve cavitation but increased lipid exchange with targeted cells.