The disposition of a constant-rate (0.3 mEq/kg/hr) intravenous potassium load was studied in anuric, chronic hemodialysis patients. Changes in plasma potassium concentration could be adequately described by a two-compartment kinetic model under both isohydric conditions and during acute metabolic alkalosis. From 63 to 92% of the infused potassium left the extracellular fluid (ECF) in isohydric studies, and from 73 to 97% left the ECF in alkalanizing studies. Cellular uptake of the infused potassium was less when the plasma potassium concentration was higher. Plasma aldosterone levels rose but insulin levels did not increase during infusions. In a juvenile-onset diabetic subject, the impairment of cellular potassium uptake at higher plasma potassium was magnified so that infused potassium was virtually confined to the ECF compartment until exogenous insulin was given. This implies a permissive rather than a regulatory role for endogenous insulin in facilitating cellular entry of excess potassium.