Using inhibitors of gluconeogenesis (phenylpyruvate, alpha-cyano-4-hydroxycinnamate, quinolinate, D-malate, aminooxyacetate), we analysed mechanisms by which the gluconeogenic substrates, lactate and pyruvate, as well as a short-chain fatty acid, acetate, stimulate the uptake of a weak organic acid, fluorescein, in the rat kidney. We have shown that these inhibitors modified both the rate of glucose production from lactate and pyruvate in the renal cortex fragment suspension and the stimulatory effects of the metabolic substrates on fluorescein uptake in superficial proximal tubules in the renal cortex slices. The peculiarities of the effects of lactate and pyruvate on the uptake were correlated with the partial divergence of the pathways of gluconeogenesis from these precursors. The linkage of the weak organic acid uptake with gluconeogenesis is interpreted in terms of the hypothesis that the uptake is controlled by the cytoplasmic pyridine nucleotide redox potential, which is maintained with the participation of certain processes involved in glucose synthesis.