Abstract Background. Thermal events during extracorporeal venovenous perfusion-induced systemic hyperthermia (VV-PISH) were studied and related to determination of whole-body and regional thermal isoeffect doses. Methods. Swine ( n=6, 77 ± 4.5 kg) were heated to a target temperature of 43°C for 120 minutes using VV-PISH. Colored microspheres were injected during preheat, heat induction, maintenance, cool down, and after decannulation. The esophageal, tympanic, rectal, pulmonary artery, bladder, bone marrow, kidney, brain, blood, lung, and airway temperatures were recorded continuously. The thermal dose, thermal exchange, metabolic heat production, heat loss to the environment, the change in body heat, and the thermal isoeffect dose were studied at 15-minute intervals. Results. VV-PISH increased heart rate and cardiac output and caused a redistribution of blood flow favoring the thoracoabdominal organs. Greatest thermal exchange occurred during the heating phase (total 2,162 ± 143 kJ), metabolic heat production contributed in all phases (274 ± 9 kJ), the greatest change in body heat occurred during heating (1,310 ± 309 kJ) with a total delivered thermal dose of 298 ± 21 kJ, and the total whole body thermal isoeffect dose at 100 ± 5 minutes. Conclusions. VV-PISH is feasible, is capable of transferring sufficient heat, causes a redistribution of blood flow favoring the thoracoabdominal organs, and facilitates calculation of whole-body and regional thermal isoeffect doses.