This application's long term objective is to determine the potential for diagnostic ultrasound to induce biological effects in mammalian tissues. To accomplish this objective, several approaches are proposed; 1) to determine for extra utero human placentas the size and quantily of gas nuclei and the ultrasound parameters (IM, frequency, prr) needed to activate the nuclei to acoustic cavities; 2) to determine (a) the role of intercellular space and gas in mediating acoustic cavitation in an in vitro multicellular tissue system (multicell spheroids), to measure the force requisite for bubble penetration of cells, (c) to determine whether acoustic cavitation occurs intracellularly; 3) to verify certain phenomenological reports regarding ultrasound-induced effects (sister chromatid exchanges, unscheduled DNA systhesis, cell transformation, multigeneration cell deformation) in certain in vitro systems and, if verified, to identify the physical mechanism of action causing the effects(s); 4) to investigate the postulate that at hyperthermic temperatures a non-cavitational, non-thermal ultrasound-induced mechanism is operative; and 5) to determine the most effective pulsing regimes (prr, frequency) for induction cavitation at ultrasound intensities (Im) comparable to those emitted by clinical diagnostic units. The results obtained should be directly relevant to assessments of the potential for diagnostic ultrasound to induce biological effects in human tissue. Because the proposed projects focus on understanding how certain effects in chemical, in vitro, and vivo mammalian systems are produced (i.e., mechanisms) the results from these areas may be extrapolated to broader question of health and safety from exposure to dignostic ultrasound.