The mechanism by which dietary K<sup>+</sup> restriction induces distal–nephron Li<sup>+</sup> reabsorption was investigated by administration of bendroflumethiazide (BFTZ) or vehicle in conscious Wistar rats. Changes in fractional excretion of Li<sup>+</sup> following administration of amiloride (ΔFE<sub>Li</sub>) were used as an index of distal tubular Li<sup>+</sup> reabsorption. The results revealed an absence of distal tubular Li<sup>+</sup> reabsorption in K<sup>+</sup>–replete rats (ΔFE<sub>Li</sub> = 3.6±2.4%), in contrast to K<sup>+</sup> restriction in which ΔFE<sub>Li</sub> was 24.0±2.7%. The distal tubular Li<sup>+</sup> reabsorption in K<sup>+</sup>–depleted rats was significantly reduced by preadministration of BFTZ (ΔFE<sub>Li</sub> = 9.2±0.9%). The fractions of Li<sup>+</sup> and Na<sup>+</sup> reabsorbed in the amiloride–sensitive segment were different in K<sup>+</sup>–replete rats (9±6 vs. 60±6%), but similar in K<sup>+</sup>–depleted rats (61±5 vs. 73±4%). BFTZ administration to K<sup>+</sup>–depleted rats resulted in a proportional decrease in these fractions, suggesting competition between Na<sup>+</sup> and Li<sup>+</sup> for reabsorption in the distal–nephron segment during K<sup>+</sup> depletion. These results are compatible with the hypothesis that during K<sup>+</sup> depletion the reabsorption of Li<sup>+ </sup>in the distal–nephron segment is competitively inhibited by Na<sup>+</sup>.