This study was to investigate whether the apoptosis in isolate sarcoma 180 (S180) cells could be enhanced by ultrasound in the presence of protoporphyrin IX (PPIX) and also to evaluate the underlying biologic mechanism. S180 cells were exposed to ultrasound for 30 seconds' duration, at the frequency of 2.2 MHz and an acoustical power of 3 W/cm(2) with 120 microM of PPIX. Cell apoptosis was evaluated based on the morphologic changes at different incubation times after sonication. Our results showed that the apoptosis in S180 tumor cells were induced by exposure, and the rate of apoptosis rose gradually with a longer incubation time. Our results also showed that changes in Fas protein expression were correlated with the development of apoptosis. The activities of caspase-8 and -3 were apparently upregulated by apoptosis, and the death substrate (PARP) was cleaved to active segments in a time-dependent manner. These results indicated that PPIX-mediated sonodynamic effect could exert its antitumor effect by triggering apoptosis in S180 cells through a Fas-mediated signal transduction pathway.