Renal Na⁺ and K⁺ excretion was measured in rats with varying dietary K⁺ intake. The requirement for channel-mediated distal nephron Na⁺ reabsorption was assessed by infusing the animals with the K⁺-sparing diuretic amiloride via osmotic minipumps. At infusion rates of 2 nmol/min, the concentration of amiloride in the urine was 38 μM, corresponding to concentrations of 9–23 μM in the distal tubular fluid, sufficient to block >98% of Na⁺ transport through apical Na⁺ channels (ENaC). With a control K⁺ intake (0.6% KCl), amiloride reduced K⁺ excretion rates (U_KV) from 0.85 ± 0.15 to 0.05 ± 0.01 μmol/min during the first 2 h of infusion, suggesting that distal nephron K⁺ secretion was completely dependent on the activity of Na⁺ channels. When K⁺ intake was increased by feeding overnight with a diet containing 10% KCl, amiloride reduced U_KV from 7.5 ± 0.7 to 1.3 ± 0.1 μmol/min despite an increased plasma K⁺ of 9 mM, again suggesting a major but not exclusive role for the Na⁺ channel-dependent pathway of K⁺ secretion. The maximal measured rates of amiloride-sensitive K⁺ excretion correspond well with estimates based on apical K⁺ channel activity in distal nephron segments. However, when the animals were adapted to the high-K⁺ diet for 7–9 days, the diuretic decreased U_KV less, from 6.1 ± 0.6 to 3.0 ± 0.8 μmol/min, indicating an increasing fraction of K⁺ excretion that was independent of Na⁺ channels. This indicates the upregulation of a Na⁺ channel-independent mechanism for secreting K⁺.