Recent investigations of pulsed ultrasound at high acoustic intensities have revealed a regime in which significant breakdown of tissue structure can be achieved. This therapeutic modality, which might be termed histotripsy, is dependent on the presence of highly active cavitation evidenced by significant temporal fluctuations in acoustic backscatter. In the presence of tissue interfaces, erosion can result yielding, for example, well-defined perforations potentially useful in creating temporary shunts for the treatment of hypoplastic left heart syndrome. When applied in bulk tissue, the process results in a near emulsification with little structural integrity remaining or chance of cellular survival. In each case, the process is dependent on acoustic parameters of the field to not only produce damage for a given pulse but also to sustain the cavitation nuclei population for subsequent pulses. Fluctuations in acoustic backscatter indicate both initiation and extinction of the appropriate cavitation activity during application of therapeutic ultrasound, which leads to a potential feedback mechanism to minimize acoustic exposure. This presentation will discuss the observed tissue damage as affected by acoustic parameters and the ability to monitor the presence of cavitation activity expected to be responsible for these effects. [Work supported by NIH grants RO1 RR14450.]