The potential for the use of hyperthermia in the treatment of cancer is based on a strong and compelling biologic rationale. In the laboratory it has been shown in quantitative assays both in vitro and in vivo that (1) hyperthermia is cytotoxic to tumor cells as a function of time at temperatures above 42 degrees C; (2) cytotoxicity is relatively high for radioresistant S-phase cells and for cells that are nutritionally deprived and acidotic, conditions one might expect in regions of tumors containing large numbers of radioresistant hypoxic cells; and (3) heat is a radiosensitizer and a chemosensitizer. Clinical study is hampered by less than optimal physical heating methods and the need for invasive thermometry. Ultrasonic and electromagnetic approaches each have limitations and advantages. In spite of technical limitations, efficacy has been shown for superficial tumor sites treated by local hyperthermia and Phase I studies are underway investigating the more complicated problem of deep regional hyperthermia. Although whole body hyperthermia has the attractive capability of treating metastatic as well as more localized cancer, it is toxic therapy and its role in treatment remains undefined. Research advances in equipment design and treatment optimization are needed; however, there are studies underway utilizing existing methods and rationale which should further clarify the potential clinical usefulness of regional hyperthermia in combined modality approaches to cancer therapy.