Ultrasound accelerates fibrinolysis in vitro at intensities that are potentially applicable clinically to enhance thrombolytic therapy. To extend these findings in vivo, the effects of ultrasound on fibrinolysis induced by streptokinase have been examined in two rabbit models. In a rabbit model of fibrinolysis in small vessels, scalpel cuts were made in the ear and rabbits were then rested 2 h to allow maturation of hemostatic plugs. Bleeding occurred when clots in small ear vessels were lysed during thrombolytic therapy. In a prospective study, administration of streptokinase alone results in bleeding after 18(plus or minus)3 min (mead (plus or minus) SEM), but addition of ultrasound (1 MHz, 1 W cm[sup -2] and a 50% duty cycle) shortened the time to bleeding to 7(plus or minus)4 min (p<0.05). The effect of ultrasound was also examined in a rabbit arterial thrombolysis model and, thrombolysis occurred in 9/17 (53%) of animals receiving both streptokinase and ultrasound, and this was significantly greater than the rate in animals receiving streptokinase alone (2/15, 13%, p=0.025). Light and electron microscopic examination revealed minor changes in platelet accumulation on the thrombus and minor changes in the vessel intima of ultrasound-exposed vessels. These findings indicate that externally applied ultrasound accelerates fibrinolysis in vivo.