The efficiency of high-frequency destruction of microbubble-based contrast agent is limited by the high pressure threshold, while the difficulty of spatially confining destruction induced by low-frequency excitation to a small sample volume potentially increases the risk of adverse bioeffects. The dual-frequency excitation method involves the simultaneous transmission of 2 high-frequency sinusoids to produce an envelope signal at the difference frequency. The envelope signal provides the low-frequency driving force for oscillating the contrast-agent microbubbles to improve destruction efficiency, while the destruction sample volume remains small due to the high frequency of the carrier signal. Experimental results indicate that dual-frequency excitation consistently results in destruction of contrast-agent microbubbles that is superior to using a tone burst at the carrier frequency. With 1 micros pulse length, the acoustic pressure threshold for 95% microbubble destruction markedly reduces from 2.6 MPa to 0.9 MPa when the dual-frequency pulse having envelope frequency of 3 MHz is utilized instead of the 10-MHz sinusoidal pulse. In addition, the dual-frequency pulse having lower envelope frequency generally provides more efficient microbubble destruction, especially when the excitation waveform is long enough to guarantee sufficient envelope component.