The synergistic effects of hyperthermia (temperatures > or = 41 degrees C) when combined with radiotherapy or cytotoxic drugs, as well as a modulation of tumour-related immunological phenomena have been demonstrated preclinically. Local or regional hyperthermia in combination with radiation or chemotherapy has been studied in patients during recent years, and has convincingly demonstrated that hyperthermia is feasible and tolerated by patients. Furthermore, there is strong evidence that hyperthermia may provide an improvement in local control as compared with radiotherapy or chemotherapy alone. Systems based on radiowave irradiation allow sufficiently tolerable and effective regional hyperthermic therapy in patients with rectal carcinomas. Used as part of curative pre-operative and postoperative multimodal therapeutic strategies in high-risk patients with locally advanced rectal carcinomas, hyperthermia may result in improved local control and a higher rate of sphincter-sparing procedures. 20 patients with non-resectable, locally advanced primary or recurring rectal carcinoma T3/4 entered a phase I/II study of pre-operative radiochemothermotherapy with folinic acid and 5-fluorouracil, radiation (45 Gy HD), as well as regional hyperthermia once a week followed by chemotherapy after surgery. The regimen proved to be sufficiently tolerable. Acute grade III or IV toxicities did not occur after hyperthermia. Tumour resections were performed on 14 of the 20 patients, with 13 being complete. In 9 of the carcinomas, downstaging compared with the pretherapeutic stage was achieved. In 3 of 6 patients with persistent non-resectable tumours, local control has now been maintained for more than 12 months. One patient progressed locally during neoadjuvant combination therapy. These results prompted the initiation of a prospective randomised study to evaluate the relative importance of regional hyperthermia in this setting.