The renal collecting duct serves the fine-tuning of renal acid-base excretion and regeneration of bicarbonate. Type A intercalated cells excrete protons and ammonium thereby generating new bicarbonate replenishing bicarbonate lost during metabolism. In contrast, type B intercalated cells secrete bicarbonate into urine, a process coupled to reabsorption of chloride via pendrin. Both, acid excretion and as well as bicarbonate-dependent chloride reabsorption by type A intercalated cells or type B intercalated cells, respectively, are directly and indirectly regulated by the renin-angiotensin II – aldosterone system. Impaired aldosterone dependent regulation leads to hypotension as well as to type IV distal renal acidosis with hyperkalemia. The molecular basis of the aldosterone effects on acid-base transport in the collecting duct is only partially understood We will discuss three mechanisms by which aldosterone affects the function of type A and B intercalated cells. First, aldosterone exerts indirect effects on proton secretion by type A intercalated cells by enhancing the expression and activity of the epithelial sodium channel ENaC in neighboring principal cells. Sodium absorption generates a more lumen-negative potential that drives both potassium secretion by principal cells as well as proton secretion by type A intercalated cells. The connecting tubule is the main site of this interaction. Second, all subtypes of intercalated cells express the mineralocorticoid receptor but only low levels of the cortisone-metabolizing enzyme 11beta-hydroxy steroid dehydrogenase II. In these cells, aldosterone but not cortisone stimulates H+-ATPase-dependent proton secretion within 5 minutes. This rapid effect is most likely independent from the mineralocorticoid receptor, involves and requires an elevation of intracellular calcium and is mediated by a PKC dependent pathway leading to the remodeling of the luminal membrane with extensive extrusions and accumulation of proton pumps. However, the long-term effects of aldosterone most likely involving genomic regulation via the mineralocorticoid receptor are not very well characterized. Thirdly, aldosterone stimulates chloride reabsorption by type B intercalated cells through enhanced mRNA and protein expression of pendrin. Pendrin mediates chloride absorption in parallel to sodium absorption by ENaC and enhances also the expression of ENaC, possibly through affecting the local pH environment. In summary, aldosterone exerts complex effects on the collecting duct linking electrolyte and acid-base handling. Some of the effects of aldosterone appear to be mediated by non-classic non-genomic pathways that require further characterization to elucidate the underlying molecular mechanisms and their relevance to overall aldosterone actions.