The cortical collecting duct (CCD) is capable of secreting H<sup>+</sup> or HCO<sup>–</sup><sub>3</sub> depending on the acid-base status in vivo. Transport is a function of two types of intercalated cells in the CCD: A-intercalated cells secrete H<sup>+</sup> and B-intercalated cells secrete HCO<sup>–</sup><sub>3</sub>. Metabolic acidosis results in a decrease in HCO<sup>–</sup><sub>3</sub> secretion and an increase in H<sup>+</sup> secretion by the respective cells. Using a model of metabolic acidosis in vitro, we have shown that the down-regulation of HCO<sup>–</sup><sub>3</sub> secretion occurs by endocytosis of apical anion exchangers in B-intercalated cells. The finding of basolateral anion exchangers in some adapted B-intercalated cells is consistent with a reversal of functional epithelial polarity. Plasticity of polarity is also observed in cultured intercalated cells: high-density plating results in converting B- to A-intercalated cells via the deposition of the novel protein hensin in the extracellular matrix. A key problem in renal physiology is to investigate the role of hensin in mediating the adaptation of the CCD to acidosis in vitro and in vivo.