To evaluate the efficacy of intra-arterial chemotherapy combined with hyperthermia for metastatic liver cancer, our cooperative study group carried out a randomized clinical trial comparing intra-arterial chemotherapy alone and intra-arterial chemotherapy combined with hyperthermia. Patients were treated with combined chemotherapy of epirubicin (EPIR), mitomycin C (MMC), 5-fluorouracil (5-FU), by hepatic infusion using a subcutaneously implanted reservoir. Hyperthermia (8MHz radiofrequency) was usually performed for 40-60 min every week, and intra-arterial chemotherapy was performed immediately before hyperthermia. Twenty-six patients were registered by telephone contact and allocated at random to groups treated with either intra-arterial chemotherapy alone (14 patients) or combination therapy (12 patients). The response rate was 7% in the chemotherapy alone group (1 PR among 14 evaluable patients), and 40% in the combination therapy group (4 PR among 10 evaluable patients). Our results suggest that intra-arterial chemotherapy combined with hyperthermia is a useful modality for the treatment of metastatic liver cancer.