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The anesthetic effects of ketamine and its distribution to CNS tissue were examined in rats following intravenous administration. Peak brain levels of ketamine were achieved less than a minute following injection. At all times studied, brain:plasma ratios of ketamine were 6.5:1. Study of regional brain levels indicated a preferential distribution of ketamine to the cerebral cortex 30 seconds and one minute after injection. The x-de-methylated metabolite of ketamine also accumulated in the brain, reaching levels appreciably higher than that in plasma 10 minutes after administration. No evidence of the presence of the other metabolite, the cyclohexanone oxidation product, was found in either plasma or brain. Studies of biotransformation in citro showed that brain tissue was incapable of metabolizing ketamine, while liver homogenates metabolized ketamine to the x-demethylated product exclusively. These observations on the disposition of ketamine and its metabolite are discussed in relation to the diverse actions of this dissociative anesthetic agent in the central nervous system.