We studied in vitro the efficacy of ultrasound in human blood clot disruption, as well as the effects of clot age, wire probe length, and streptokinase on the outcome. The study included sizing the resulting particulate debris. Clot age (1 to 7 days) had no effect on the time required for disruption. Three groups of 1-day-old clots (n = 10 for each) were exposed to the same ultrasonic power source via probes of different lengths. The time required for clot disruption varied approximately as the square of the length for probes of 31, 56, and 105 cm, but was less than 3 minutes even for the longest probe employed. Disrupted whole-blood clot as well as cell-free fibrin clot solutions were analyzed for particulates by the resistive-pulse technique (size range: 2.5 to 80 microns). Debris as large as 80 microns were seen after disruption of whole blood clots, while cell-free fibrin clots contributed little above 40 microns. In all size ranges, whole blood clots produced two orders of magnitude more particulates than cell-free fibrin clots. Addition of streptokinase (7500 U/mL) had little effect on the size distribution of debris, with 99% of all particulates being smaller than 10 microns. D-dimer analysis was performed on the dissolved cell-free fibrin clots with and without streptokinase. While the former had analytically higher D-dimer concentrations than the latter (from eight- to 16-fold), the levels in both cases would be below detectability if measured in vivo. Hence the present study supports the concept that ultrasound can be employed to disrupt human blood clots by mechanisms (mechanical and cavitational) other than fibrinolysis.