We examined experimentally and clinically the effect of misonidazole (MISO), a hypoxic cell radiosensitizer, in combination with hyperthermia. First, tissue blood flow and tumor growth of xenoplanted human gastric cancer in nude mice were measured after treatment with MISO 500 mg/kg ip plus hyperthermia at 40.5, 42.0 and 43.5 degrees C. Also clinically, 17 advanced gastric cancer patients with peritoneal seeding underwent intraperitoneal hyperthermic perfusion (IPHP). They were given MISO 1.45 g/m2 po twice (12 hours and 5 hours before IPHP). And plasma MISO levels were measured. MISO plus hyperthermia produced a more prolonged decrease of the tumor blood flow than hyperthermia alone. At 43.5 degrees C, TbF recovered 2 days after the treatment. MISO plus hyperthermia also made tumor growth delay more marked than hyperthermia alone. In gastric cancer patients treated with MISO plus IPHP, T 1/2 of serum MISO was 7.7 hours and the AUC was 1,087 micrograms.hr/ml. There were no side effects observed which were caused by MISO. Thus MISO can be an effective thermosensitizer when used in combination with hyperthermia.