MAT B III cells were insonified at ultrasound frequencies of 1.15 and 2.25 MHz in the presence of different ultrasound contrast agents (UCA) and a plasmid encoding for the green fluorescent protein. The transfection efficiency was assessed by flow cytometry, while contrast agent destruction by ultrasound was evaluated using optical and scanning electronic microscopies. It was found that the gas and shell properties of the UCA have an important influence on cell transfection. A good correlation was observed between bubble destruction and transfection rate, and it was demonstrated, for the first time, that hard-shelled contrast agents (gas microcapsules) are promising candidates for ultrasound-mediated gene delivery.