The potential application of ultrasonic energy for ablation of atherosclerotic plaques was studied in human atherosclerotic arteries with continuous and pulsed delivery of energy. With a prototype ultrasonic wire probe (n = 79 segments), there was gross reduction in vascular lesions as well as microscopic disruption of fibrous and calcified plaques. Normal portions of vessels appeared unaffected by the application of ultrasound. The prototype ultrasonic wire catheter ablated calcific deposits in less than 10 seconds. With this probe, all 26 complete atherosclerotic occlusions 0.5-5 cm in length were recanalized irrespective of the presence of calcium. Twenty-four of the segments were reopened in less than 20 seconds. By light microscopy, the site of plaque ablation was smooth, concave, and conformed to the shape of the probe tip. In 17 samples, there was evidence of thermal injury, and in six of the 79 samples studied with the prototype probe, there was vascular perforation. No vascular perforation occurred without thermal damage, when pulsed (rather than continuous) ultrasonic energy was used (n = 40) or when the duration of application was less than 30 seconds, with power output less than 25 W and with the probe oriented parallel to the wall (n = 26). Thus, by modifying the duration, mode, and magnitude of the ultrasonic power output, thermal injury and vascular perforation may be avoided. In vivo intra-arterial ultrasonic angioplasty of a canine chronic femoral fibrocellular occlusion was also performed. A preliminary in vivo study demonstrated feasibility of the percutaneous application of intra-arterial ultrasonic recanalization. Thus, ultrasonic energy appears to have potential as a method for ablation of occlusive atherosclerotic plaque.