Hypothermia results in a progressive depression of cerebral electrical activity and metabolism. In the setting of cerebral ischemia, large reductions in temperature are associated with a better preservation of high-energy phosphates, a reduced accumulation of toxic metabolites, and an improvement in post-ischemic outcome. With temperature reductions of < or = 6 degrees C, the brain is also partially protected from ischemic neurologic injury; however, this protection does not correlate with measurable alterations in high-energy phosphate depletion or lactate accumulation. Thus, cerebral protection by hypothermia may be due to a variety of factors, including alterations in basal metabolism, ion homeostasis, agonist-specific receptor activity, and cellular structure. Further, the relative influence of these factors may change with progressive reductions in temperature.