Response of cells i n vitro a n d of intact tissue in vivo, both of normal a n d malignant origin, to moderate levels of hyperthermia has been reviewed. Abundant laboratory and clinical evidence exists which demonstrates that tolerable levels of hyperthermia (locally applied) can regularly effect a delay in tumor growth, often a complete regression, a n d occasionally a permanent control of tumor. This means that in some tumors, aerobic and hypoxic cells are inactivated by the heat applied. Further, moderate hyperthermia is a potent sensitizer to ionizing radiation. T h e mechanism of action of hyperthermia remains unknown; however, there is prompt suppression of DNA, RNA, and protein synthesis, reduction of oxygen consumption, labilization of lysozymes, etc. Effect of heating is strongly correlated with temperature level: a n increase in temperature by 1 degree C reduces time for a specified response by a factor of 2. Application of local, regional, or systemic hyperthermia to the human cancer patient alone or in combination with radiation or certain drugs may be considered as attractive potential therapy modality. At present, information about relative thermal sensitivity of normal and tumor tissue is scant. This appears to be a good area for preclinical research.