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Rats were given a portocaval anastomosis and 3 weeks later, when the only ultrastructural change in the CNS is watery swelling of astrocytes. several aspects of brain metabolism were studied. The uptake of leucine by the brain, its incorporation into protein and its oxidation were followed after the simultaneous injection of a mixture of ~-[l-'~C]leucine and ~-[4,5-~H]leucine. The concentration of leucine in blood was lowered in the operated animals whereas in brain it was increased. The specific radioactivity of leucine in the brain was comparable to values in control animals and there was no evidence of a decrease in incorporation of [l-'4C]leucine into brain proteins over the short experimental time period studied. The only difference from the controls in the oxidation of [4,5-3Hfleucine was a greater accumulation in glutamine. The amount of glutamine in the brains of the operated animals had increased 4-fold at the time of the metabolic studies.From dual-labelled experiments in which a mixture containing [1-14C]butyrate and ~-[4,5-'H]leucine was injected intravenously, it was shown that, in both control and operated animals, the pools of brain glutamate and glutamine labelled from butyrate were metabolically distinct from those labelled from leucine. The total radioactivity appearing in brain from [l-' 4C]butyrate was markedly reduced in operated animals, but the radioactivity from ~-[4,5-~H]leucine was not.The metabolism of [1-'4C]octanoate was compared with that of [1-'4C]butyrate. In control animals the labelling of metabolites was almost identical with either precursor. In operated animals there was no reduction in the uptake of [1-'4C]octanoate into the brain. There was evidence that the size of the glutamine pool labelled, relative to glutamate, was increased but that it had a slower fractional turnover coefficient. A link between astroglial changes and an impairment to the carrier mechanism for transport of short chain monocarboxylic acids across the blood-brain barrier is suggested.RATS given a portocaval anastomosis survive for many months, although they show during the first 4 weeks a marked loss in body weight. The chronic exclusion of the liver from the portal circulation is known to lead to morphological changes in central nervous tissue in man and animals and the sequence of these changes in rat brain have been described by ZAMORA et al. (1973). During the first few weeks after the operation ultrastructural changes are confined to the astroglial cells which have a swollen, watery appearance throughout their cytoplasm. Later, the astroglia show a reactive response with increases in the amount of smooth membrane, numbers of mitochondria, ribosomes and electron density of the cell's cytoplasm related to degeneration of axons in the neuropil. The relationship between these morphologi-

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