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