To identify the temperature dependent change of the apparent diffusion coefficient (ADC) of water in brain tissue, the ADC values of normal rat brain were measured over a range of body temperatures with monitoring of head temperature using a small water reference implanted under the temporalis muscle. An initial experiment using thermocouples implanted into the cortex, caudate-putamen, temporalis muscle, and rectum demonstrated that temperature in all regions were highly correlated over a temperature range from 33 to 39 degrees C. In another group of normal rats, brain ADC values varied almost uniformly with body temperature over the temperature range 33-39 degrees C, implying that brain ADC values accurately reflect changes in brain temperature. The effects of focal ischemia and administration of the noncompetitive N-methyl-D-aspartate (NMDA) antagonist, CNS-1102, on ADC were also examined, using the suture middle cerebral artery (MCA) occlusion model while maintaining the body temperature at 37 degrees C. ADC values and therefore brain temperature in the nonischemic and ischemic hemispheres were not affected by the drug. These experiments suggest that brain ADC measurement could be useful in animal studies and, potentially, in humans to assess the effects of pharmacologic intervention on brain temperature.