The renal proximal tubule of vertebrates performs an essential role in controlling plasma SO42- concentration ([SO42-]). Although net tubular SO42- reabsorption is the predominate control process in terrestrial vertebrates, a facilitated secretory flux is also present. In contrast, marine teleosts obtain excess SO42- from drinking, and increased plasma [ SO42-] is prevented predominately through net tubular secretion. Tubular SO42- secretion is accomplished by at least two electroneutral anion exchange processes in series. Movement of SO42- into the cell across the basolateral membrane is pH dependent, suggesting SO42-/OH- exchange. Luminal HCO3- and Cl- can facilitate SO42- movement out of the cell across the brush-border membrane. The molecular identities of the anion exchangers are unknown but are probably homologues of SO42- transporters in the mammalian SLC26 gene family. In all species tested, glucocorticoids increase renal SO42- excretion. Whereas glucocorticoids downregulate SO42- reabsorptive mechanisms in terrestrial vertebrates, they may also stimulate a mediated secretory flux. In the marine teleost, cortisol increases the level of SO42-/HCO3- exchange at the brush-border membrane, tubular carbonic anhydrase (CA) activity, CAII protein, and a proportion of tubular SO42- secretion that is CA dependent. CA activity is required for about one-half of this net SO42- secretion but is also required for about one-half of the net reabsorption in bird proximal epithelium. A CA-SO42-/anion exchanger metabolon arrangement is proposed that may speed both the secretory and reabsorptive processes.