The relative importance of renal versus extrarenal mechanisms in the impaired potassium homeostasis in the various stages of chronic renal failure remains undefined. We evaluated potassium homeostasis after an acute oral load of potassium chloride (0.25 mEq/kg body weight) in 10 patients with end-stage renal disease on chronic hemodialysis and 8 control subjects. The maximal increment in plasma potassium concentration in the patients (1.06 +/- 0.13 mEq/1) was significantly higher than that of controls (0.39 +/- 0.1 mEq/1). When expressed as a percentage of the retained load, the patients translocated less potassium into cells (21 vs. 51%). Four of the patients exhibited no apparent transfer of potassium into cells, all the administered load remaining in the extracellular fluid compartment. The extrarenal abnormality does not appear to be related to acidemia, hyperglycemia, or abnormalities in insulin secretion. We conclude that patients with end-stage renal disease undergoing hemodialysis exhibit impaired extrarenal mechanisms of potassium disposal.