The collecting duct is responsible for the final secretion or reabsorption of protons and bicarbonate, respectively. Approximately 2% of the total filtered bicarbonate is reabsorbed in this segment. At least two different types of cells are involved in the transport of protons and bicarbonate, namely, type A and B intercalated cells. Their relative abundance differs in zonal distribution in the collecting duct. A variety of transport proteins and enzymes take part in the transcellular movement of protons and bicarbonate, some of them identified on a molecular level. These proteins are tightly regulated by hormones such as angiotensin II, aldosterone or endothelin or by the metabolic status of the organism. Alterations in acid-base intake or electrolyte status have profound effects on the collecting duct. Moreover, drugs interacting with renal electrolyte or bicarbonate handling (i.e. diuretics, glucocorticoids) also often affect acid-base transport in the collecting duct. For some of the identified proteins mutations have been found in various genetic diseases and syndromes of distal renal tubular acidosis leading to metabolic acidosis and an increased risk of nephrocalcinosis or -lithiasis.