The objective of this study was to develop an in vitro method to investigate the effect of ultrasound on the in vitro absorption of ibuprofen from a propylene glycol/water vehicle through human epidermis. A diffusion cell was modified so ultrasound could be applied to the vehicle and skin. Since ultrasound can increase the temperature underneath the area of application, control representing temperature effects ran concurrently to the ultrasound experiment. The results demonstrate that ultrasound can increase the penetration of ibuprofen through human skin. This increase in diffusion was greater than for controls where an equivalent increase in temperature was utilized. The results also indicate that evaporation of vehicle components may alter the skin/vehicle partition coefficient, decreasing the effects of ultrasound on the penetration of ibuprofen through the skin.