In 21 uraemic subjects not yet requiring dialysis, the serum values of citrate, fumarate, oxalacetate and malate were significantly increased, so that the sum of the concentrations of the TCA-cycle intermediates were increased threefold compared to that of 18 control subjects. The replenishment of TCA intermediates could, in theory, occur by several anaplerotic reactions, mainly those catalysed by pyruvate-carboxylase and malic enzyme. The overall pattern detected in uraemic patients is similar to that observed in rat skeletal muscle during exercise, in which increased acetyl CoA has been found.