Gas bubbles of sufficient size to serve as cavitation nuclei may form spontaneously in tissue in regions of very low interfacial tension. In the absence of an acoustic wave or other mechanical stress, such nuclei will quickly dissolve and disappear from the medium. Under the influence of an acoustic wave, however, these microbubbles may grow to many times their initial size and then collapse violently, a process known as inertial cavitation. In this work, the in vivo energetics and dynamics of the nucleation-cavitation process were modeled by treating tissue as a homogeneous fluid. The assumption of a viscosity of 10(-3) Pa s (i.e., that of water) resulted in the lowest acoustic rarefactional pressure threshold for nucleation-cavitation events, similar to4.0 MPa, which was essentially frequency-independent over the range 1 to 15 MHz. The rarefactional pressure threshold for a viscosity of 5 x 10(-3) Pa s (that of blood) also was -4.0 MPa at 1 MHz, but the threshold for this higher viscosity increased nearly linearly with frequency above similar to5 MHz, never being more than similar to0.2 MPa below the equivalent derated peak rarefactional pressure calculated assuming MI = 1.9, the current USFDA guideline. (E-mail: cchurch@olemiss.edu) (C) 2002 World Federation for Ultrasound in Medicine Biology.