The rosy mutants of Drosophila melanogaster recapitulate the features of xanthinuria type I, an autosomal recessive disease of purine metabolism, with xanthine nephrolithiasis (kidney stones) of the Malpighian (renal) tubules (Wang et al., 2004; Kamleh et al., 2008). It is thus of interest to establish whether the more common calcium oxalate nephrolithiasis can also be modeled in this organism. When fed on sodium-oxalate enhanced diet, flies develop more slowly; and the tubule lumen becomes occluded with crystalline inclusions, suggesting that oxalate handling, and stone formation, may be similar in flies and humans. SLC26 transporters are anion transporters with diverse substrate specificity. They are expressed mainly in epithelia and play a central role in secretion and absorption of anions such as chloride, oxalate (ox^2-), sulfate (SO₄^2-), bicarbonate (HCO₃^–), iodide, formate and hydroxyl. Slc26a6 is expressed in kidney and gut epithelia, and mediates electrogenic Cl^–/ox^2-, Cl^–/HCO₃^– or Cl^–/SO₄^2- exchange. Slc26a6 seems to be the dominant Cl^–/ox^2- exchanger of the proximal tubule brush border and small intestine, and Slc26a6 knockout mice show Ca oxalate nephrolithiasis (Sindic et al., 2007; Soleimani, 2008). Recently, the chicken and zebrafish Slc26a5 transporters (prestins) were shown to mediate electrogenic Cl^–/ox^2- and Cl^–/SO₄^2- exchange rather than being an auditory sensor. The FlyAtlas.org expression resource (Chintapalli et al., 2007) reports that Drosophila prestin (dPrestin) is expressed mainly in the gut and tubules, rather than in sensory or nervous tissue. When expressed in Xenopus oocytes, dPrestin mediates electrogenic Cl^–/ox^2- and Cl^–/SO₄^2- exchange, similar to mouse Slc26a6. Furthermore, dPrestin can mediate electrogenic Cl^–/HCO₃^– exchange. It appears that dPrestin (like mammalian Slc26a6) is associated with gut and “renal” ox^2-, SO₄^2- and HCO₃^– transport. These results lead us to speculate that Drosophila may be a useful genetic model to study the factors regulating and competing with ox^2- transport and the formation of kidney stones.