Hemolysis in vivo was demonstrated by exposing the hearts of mice to focused, pulsed ultrasound (1-MHz carrier, 10-(mu)s pulses, 100-Hz repetition frequency, 5-min total exposure time) while administering a contrast agent via tail vein. The threshold was approximately 4 MPa. This study suggests that inertial cavitation can take place in vivo if appropriate nuclei are present. However, since the degree of hemolysis in the absence of exogenous nuclei is indistinguishable from sham exposed blood with contrast agents, we must conclude that the number of spontaneous nuclei in normal blood in vivo is very small. The administration of contrast agents during lithotripsy enhanced hemorrhage in most of the tissues of the body. Thresholds for hemorrhage in the fields of a piezoelectric lithotripter were <2 MPa.