Despite the fact that SWL has been in clinical use for over fifteen years, the physical mechanisms for stone communication are still not well understood. However, there is now a growing body of experimental evidence and an evolving general acceptance by the clinical community, that SWL leads to some degree of permanent damage to treated kidneys. The mechanisms responsible for this tissue damage are also not well understood. We hypothesize that acoustic cavitation is a dominant factor in both stone comminution and kidney damage. A competing mechanism is the shear stress produced in tissue by the SWL shock wave. Acoustic cavitation results from the growth and violent collapse of cavitation bubbles produced by the SWL acoustic waveform. We have developed a set of sophisticated experimental tools that permit us to detect cavitation in a broad range of environments and with some degree of spatial and temporal resolution. Using these tools, we have acquired a significant body of evidence that demonstrates that SWL generates cavitation in both the parenchyma and the collecting system of the human kidney. We have also discovered a method of modifying an electrohydraulic lithotripter to produce a waveform that has a similar shock wave amplitude, pulse length, and acoustic energy to that of a conventional SWL waveform, but does not generate cavitation. Furthermore, we have found a way to enhance the violence cavitation collapse, as well as a way to confine cavitation to a highly localized volume. We propose to use these various discoveries and tools to ascertain to ascertain the relative roles of cavitation and shear in stone comminution and tissue damage. We have also made considerable progress toward the development of a set of theoretical models that would permit us to compute the SWL waveform at any position and time, either in vitro or in vivo. Furthermore, give a specific waveform, we can compute the response of the cavitation field to this waveform, and determine, albeit in a crude way, the potential for cavitation damage in a variety of in vitro and in vivo environments. We propose to test our hypotheses by undertaking a series of experiments in which we will apply SWL to various in vitro and in vivo models, during which we will use our cavitation detection techniques to determine the presence and location of this cavitation; later, we shall correlate the tissue damage with either the presence or absence of cavitation. We shall also undertake a series of similar experiments involving stone comminution. Using these results, we shall use our theoretical models to design a waveform that would optimize stone comminution and minimize tissue damage.