In rodents, postischemic hypothermia can provide robust and long-term functional and histological neuroprotection, even when intervention is delayed for several hours following ischemia. This generates a need to follow temperature precisely for many hours, perhaps several days if a hypothermic effect is to be studied or excluded. Such protracted temperature control (> 24 h) is difficult and often lethal when performed under general anesthesia. In awake animals, manual temperature control is safer, but exceedingly time consuming and tedious, and is impractical for large experiments. The present method allows for continuous brain temperature measurement and control in free-moving rats and gerbils. Brain temperature was measured by wireless AM probes while feedback regulation was achieved by servo-control of a lamp, fan and water misting system. Hypothermia was easily induced and maintained for 24 h at 32 degrees C in both gerbils and rats. Gerbils also tolerated 24 h at 32 degrees C followed by 24 h at 34 degrees C. This 'exposure technique' is capable of safely producing lengthy periods of mild hypothermia in rats and gerbils. Furthermore, this method can clamp temperature when temperature-altering drugs are given. For example, temperature was maintained in MK-801 drugged gerbils. The system is, therefore, eminently suitable for drug neuroprotection studies in brain ischemia.