Meclofenoxate, the p-cholorophenoxyacetic acid ester of deanol, was found to dramatically elevate choline (Ch) levels in the rat CNS. In the hippocampus, this elevation in choline was accompanied by a new elevated steady state level in acetylcholine (ACh). No such coupling was observed in the striatum or parietal cortex. Deanol also elevated choline levels in the CNS but was about half as potent as meclofenoxate; p-chlorophenoxyacetic acid was inactive in this respect. Lesions of striatal neurons with kainic acid and of hippocampal cholinergic nerve endings with surgical section of the fimbria indicated that the changes in choline levels were mainly extraneuronal. In spite of the changes in choline and ACh levels, no consistant alterations in ACh turnover were measured. In summary, meclofenoxate induced dramatic alterations in CNS choline metabolism and may, therefore, be a useful therapeutic tool for potentiating depressed cholinergic neurons.