Since ultrasound accelerates fibrinolysis and since transport of enzymes into clots is an important determinant of the rate of fibrinolysis, the effect of ultrasound on fluid permeation through fibrin gels in vitro was examined. Gels of purified fibrin were prepared in plastic tubes, and the rate of pressure-mediated fluid permeation was measured. Exposure to 1 MHz ultrasound at 2 W cm[sup -2] and duty cycle of 5 ms on, 5 ms off resulted in a significant (p=0.005) increase in flow through the gel of 29.0(plus or minus)4.2% (mean(plus or minus)SEM). The increase in flow was intensity dependent and not due to heating or fragmentation but was reduced by degassing, suggesting a role for cavitation. Scanning electron microscopy was used to examine potential effects of ultrasound on fibrin structure, which is the primary determinant of flow resistance. Fibrin gels were fixed and prepared for microscopy before, during, and after exposure to 1-MHz ultrasound at intensities from 4 to 8 W cm[sup -2]. Ultrasound caused a significant (p<0.000001) increase in fiber density and decrease in fiber diameter which was reversible when ultrasound was switched off. These results indicate that ultrasound exposure can induce a significant reversible change in fibrin structure and fluid permeation that could contribute to the ultrasonic enhancement of fibrinolysis.