A comparative study of local interstitial hyperthermia induced by low power Nd:YAG laser (laser hyperthermia) and microwave hyperthermia was carried out in vivo and in vitro in an attempt to clarify the therapeutic effect and the mechanism. Both therapies, after seven days, caused marked amounts of coagulated necroses in the transplanted tumors of human pancreatic carcinoma. Immediately after those therapies, electron microscopic examination of the tumor tissues showed membranous, cytoplasmic, nuclear and mitochondrial damage; however, this damage was much more extensive in laser hyperthermia compared to microwave hyperthermia. The cytocidal effects of heating alone, laser hyperthermia and microwave hyperthermia were also studied in vitro. Of the three, laser hyperthermia demonstrated the most notable decrease in viability. Thus, in the mechanism of laser hyperthermia, it seems that the immediate effect is cellular damage caused by both heat energy and Nd:YAG laser light followed by subsequent damage of tumor vessels.