PURPOSE: We performed invasive thermometry to verify the elevation of local temperature in the liver during hyperthermia. MATERIALS AND METHODS: Three 40-kg pigs were used for the experiments. Under general anesthesia with ultrasonography guidance, two glass fiber-optic sensors were placed in the liver, and one was placed in the peritoneal cavity in front of the liver. Another sensor was placed on the skin surface to assess superficial cooling. Six sessions of hyperthermia were delivered using the Celsius TCS electro-hyperthermia system. The energy delivered was increased from 240 kJ to 507 kJ during the 60-minute sessions. The inter-session cooling periods were at least 30 minutes. The temperature was recorded every 5 minutes by the four sensors during hyperthermia, and the increased temperatures recorded during the consecutive sessions were analyzed. RESULTS: As the animals were anesthetized, the baseline temperature at the start of each session decreased by 1.3degrees C to 2.8degrees C (median, 2.1degrees C). The mean increases in temperature measured by the intrahepatic sensors were 2.42degrees C (95% confidence interval [CI], 1.70-3.13) and 2.67degrees C (95% CI, 2.05-3.28) during the fifth and sixth sessions, respectively. The corresponding values for the intraperitoneal sensor were 2.10degrees C (95% CI, 0.71-3.49) and 2.87degrees C (1.13-4.43), respectively. Conversely, the skin temperature was not increased but rather decreased according to application of the cooling system. CONCLUSION: We observed mean 2.67degrees C and 2.87degrees C increases in temperature at the liver and peritoneal cavity, respectively, during hyperthermia. In vivo real-time thermometry is useful for directly measuring internal temperature during hyperthermia.