Recent studies of ultrasound (US) methods for targeted drug delivery and nonviral gene transfection revealed new, advantageous possibilities. These studies utilized US contrast agents, commonly stabilized microbubbles, to facilitate delivery and suggested that US delivery resulted from cell sonoporation, the formation of temporary pores in the cell membrane induced by US. Using voltage clamp techniques, we obtained real-time measurements of sonoporation of single Xenopus oocyte in the presence of Optison trade mark, an agent consisting of albumin-shelled C(3)F(8) gas bubbles (mean diameter 3.2 microm). Ultrasound increased the transmembrane current as a direct result of decreased membrane resistance due to pore formation. We observed a distinct delay of sonoporation following US activation and characteristic stepwise increases of transmembrane current throughout US duration. We discovered that the resealing of cell membrane following US exposure required Ca(2+) entering the cell through US-induced pores.