The aim of this study was to evaluate the feasibility and toxicity of a novel hyperthermic chemotherapy approach for patients with locally recurrent adenocarcinoma of the rectum. All patients were pre-irradiated (> or = 45 Gy) and had histologically proven pelvic recurrence. Hyperthermic chemotherapy was applied according to a modified 'OFF'-schedule with weekly infusions of 43 mg/m2 of oxaliplatin (i.v., 120 min), 500 mg/m2 of folinic acid (i.v., 120 min) and 2.6 g/m2 of continuous infusional 5-fluorouracil (24 h) for 6 consecutive weeks. Oxaliplatin was started in parallel to pelvic radiofrequency hyperthermia that was provided by the BSD 2000-system. A total of 67 applications were administered to nine patients and were well tolerated. A total of 55/67 (82%) chemotherapy courses were applied without dose-reduction. In 62/67 (93%) hyperthermia sessions, a treatment time of > 60 min was maintained. Tolerated power levels were on average 600 W and, thus, slightly lower than those described in curative pelvic hyperthermia schedules. Eight out of 10 episodes of severe (WHO III degrees) toxicity represented typical side-effects of the chemotherapy given (nausea n = 4, diarrhoea n = 3, neuropathy n = 1). Two severe adverse events were firstly attributable to hyperthermia (haematuria, n = 1; deterioration of a decubital ulcer, n = 1). No patient suffered WHO-disease progression during the treatment period. Two patients achieved a partial remission. It is concluded that hyperthermic chemotherapy with oxaliplatin, folinic acid and 5-FU is feasible on an outpatient basis. Overall toxicity was moderate, although hyperthermia may add side-effects to this approach. Results, moreover, suggest a relevant palliative effect in patients with pre-irradiated pelvic recurrence of rectal cancer.