Hyperthermia is becoming a potent therapeutic method for malignant brain tumors, either alone or in combination with radiation therapy. The heat response of organized tissues includes other factors besides the inherent cellular thermosensitivity, that is, tissue pH, PaO₂, and nutrient supply, all of which are largely influenced by the tissue blood flow. In this study, the regional cerebral blood flow (rCBF) changes in 15 Japanese normal monkey brains during interstitial microwave hyperthermia were investigated by the hydrogen clearance method. Under general anesthesia and controlled respiration, a parieto-occipital craniectomy, 4 × 4 cm, was performed. A microwave antenna was inserted into the brain to a depth of 2.0 cm, and the brain tissue was heated with 2450 MHz microwave irradiation. The intracerebral temperatures and rCBF were measured in the white matter 1 cm from the brain surface. During hyperthermia, the rCBF linearly increased at a rate of 10% per 1°C temperature rise. Heating at 42°C for 180 minutes resulted in a constant increase in rCBF. The perfusion rate returned to the control levels after the termination of heating. Above 45°C, the rCBF transiently increased and then started to decline during heating. No consistent results were obtained with heating at 43°C. These results show that normal monkey brain tissues respond to hyperthermia by an rCBF increase as long as the threshold values of tissue temperature (43°C) and exposure time (40-60 minutes) are not exceeded. Excessive heating may lead to irreversible damages to normal tissue and vasculature.