Ketamine produces both excitatory and depressant actions in the brain, but there have been conflicting results regarding which structures are affected and the magnitude of the alteration in cerebral metabolism produced. The authors applied the 2-[14C]deoxyglucose method quantitatively to a study of ketamine anesthesia (10 or 30 mg/kg intravenously) in the rat. Ketamine caused both increases and decreases in local cerebral glucose utilization. The areas with altered glucose utilization could be grouped into functional systems. Some structures of the limbic system showed large increases in glucose utilization; indeed the 70 per cent increases in cingulate gyrus and hippocampus were the largest of all regions examined. The extrapyramidal motor system and corpus callosum showed significant but less dramatic (20-40 per cent) increases. On the other hand, decreased metabolism occurred in the somatosensory and auditory systems, with the greatest reduction (40 per cent) in the inferior colliculus. Within some structures, such as the caudate nucleus and visual cortex, a striking redistribution of metabolism which is characterized by a change in the autoradiographic pattern of activity was noted. Reduced glucose utilization in the somatosensory and auditory systems suggests that a selective sensory deprivation occurs during ketamine anesthesia while the increased metabolism in the limbic system is consistent with neurophysiologic studies which have demonstrated seizure activity in this region. Compared with other anesthetics, which tend to produce a generalized decrease in metabolism, the cerebral metabolic effects of ketamine are unique and emphasize that it produces a state of "anesthesia" which is quite different from that of other commonly used drugs.