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 nmoles/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 µmoles/min during the first two hours 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 µmoles/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 6.4 ± 0.6 to 2.9 ± 1.0 µmoles/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⁺.