Adaptation to a high potassium diet leads to an enhanced ability to excrete an acute potassium load. The aim of this study was to examine whether the enhanced kaliuretic ability is an intrinsic renal adaptation or is secondary to extrarenal mediators such as aldosterone. Kidneys from control rats and rats on a high potassium diet were isolated and perfused in a cell-free medium (glomerular filtration rate 0.5 ml/min, fractional sodium reabsorption 95%). Feeding in the 24 h prior to perfusion had a profound effect on fractional K+ excretion in rats on high K+ (fed 1.4 +/- 0.11, fasted 0.70 +/- 0.07) but not in control (fed 0.59 +/- 0.05, fasted 0.64 +/- 0.05) rats. After feeding but not fasting, rats on high K+ had a greater fractional K+ excretion than control K+ rats. Spironolactone inhibited fractional K+ excretion in fed rats on high K+ but not in control rats (high K+ 1.45 +/- 0.18, high K+ + spironolactone 0.95 +/- 0.15; control 0.59 +/- 0.05, control + spironolactone 0.46 +/- 0.02). Although these experiments do not exclude an intrinsic renal adaptation in potassium excretion, a major component of the increased potassium excretion relates to the increased potassium intake, probably mediated via aldosterone.