Ultrasound (US) acts synergistically with thrombolytic agents, such as recombinant tissue plasminogen activator (rt-PA), to accelerate thrombolysis. Stable cavitation is highly correlated with sonothrombolytic efficacy for rt-PA-mediated thrombolysis. A review of in vitro sonothrombolysis studies utilizing a commercial US contrast agent or echogenic liposomes loaded with rt-PA to nucleate stable cavitation will be presented. Ultraharmonic signals, broadband emissions, and harmonics of the fundamental were measured acoustically using a focused hydrophone as a passive cavitation detector and utilized to quantify the level of cavitation activity. The thrombolytic efficacy of rt-PA in combination with 120-kHz US was also explored in vivo using a porcine intracerebral hemorrhagic stroke model. Clots were formed by gently infusing 3 ml of autologous blood into the frontal white matter of 28 mixed-bred Yorkshire pigs (20.5 ± 3.1 kg) and incubated for 3 hr. For these nonsurvival studies, 6 pig received rt-PA only (0.3 cc of 0.107 μg/ml), 6 received 120-kHz pulsed US alone, 6 received rt-PA plus 120-kHz pulsed US exposure, and 6 were reserved as controls (saline injection, no rt-PA and no 120-kHz US exposure). Clots treated with rt-PA alone exhibit a volume loss of 55.0% and clots treated with rt-PA and 120-kHz US have a significantly higher volume loss of 72.5% and a higher penetration of rt-PA. Thus 120-kHz pulsed US enhancement of thrombolysis has been demonstrated both in vitro and in an in vivo porcine hemorrhagic stroke model. This work was supported by NIH 1RO1 NS047603.