Ketamine appears to induce both excitatory and depressant actions in the brain; however, it is not clear which regions are affected. The 2-deoxyglucose functional mapping method of Sokoloff et al. was used to determine regional variations in metabolic activity of rat brain caused by injection of ketamine, 25-75 mg, intramuscularly. To compare the effects of ketamine with those of hippocampal-induced seizures, the 2-deoxyglucose method was used, following injection of penicillin G, 400-800 units, into the hippocampus. The findings from five control, seven ketamine-treated, and three penicillin G-treated rats are given. Ketamine caused a significant increase of metabolic activity in the hippocampal sulci and a decrease of activity in the medial geniculate and the inferior colliculus. Similar changes were found with hippocampal seizures caused by penicillin. The inhibition of the regions associated with sensory systems (medial geniculate and inferior colliculus) may account in part for the anesthetic action of ketamine, while the intense activity of the hippocampus may be related to the excitatory manifestations. The results indicate that ketamine produces seizures in the hippocampus, which in turn inhibit auditory and visually associated nuclei. Thus, the anesthesia may follow from the sensory depression and the cataleptic phenomena may be related to the hippocampal excitation.