Absorption of ammonium by the loop of Henle provides a mechanism by which ammonium produced and secreted by proximal tubules is transferred to collecting ducts in the renal medulla. Loop ammonium absorption is largely a result of active absorption of NH4+ by the thick ascending limb. Ammonium absorption in the thick ascending limb is mediated primarily by apical membrane Na(+)-NH4(+)-2Cl- cotransport, and provides a 'single effect' for countercurrent multiplication of ammonium in the renal medulla. Countercurrent multiplication causes ammonium to accumulate to high concentrations in the medullary interstitial fluid and generates a transepithelial concentration difference for NH3 that favors secretion of ammonium into medullary collecting ducts. Changes in systemic potassium balance and chronic metabolic acidosis influence ammonium excretion by regulating ammonium absorption in the medullary thick ascending limb and altering transfer of ammonium to medullary collecting ducts.