The thermal damage threshold of normal brain tissue was evaluated from immediate and delayed histological changes caused by hyperthermia treatment of normal monkey (Macaca fuscata) brains. A 2450 MHz microwave antenna and an antenna cooling system devised by our group were used for interstitial hyperthermia treatment. The antenna within the cooling system was inserted through a small craniectomy under general anesthesia. The temperature at a reference point, 4 mm radially away from the surface of the cooling system, was maintained at 42, 43, 44, 45, or 46°C for 60 minutes. Eighteen animals were treated and sacrificed immediately after the treatment, while nine animals were treated and sacrificed 7 days after the treatment. The histological changes were studied microscopically on sections stained with HE or Kluver-Barrera''s method. The non-survival experiment demonstrated that areas heated at 44°C or below showed no obvious irreversible changes. The survival experiment showed areas heated at 44°C or above developed coagulative necrosis. These histological findings indicate that thermal damage occurs in normal brain tissue after heating at 44°C or above for 60 minutes, suggesting that the safety limit for brain hyperthermia is 43°C for 60 minutes.