KCl cotransporters help maintain cellular osmotic homeostasis, but little is known about their role in the kidney. Melo et al. report that two such cotransporters, KCC3 and KCC4, function in the proximal tubule and collecting duct, respectively. The authors analysed KCC3 and KCC4 mRNA and protein expression in the kidneys of rats and mice exposed to hyperglycaemia, a low salt diet, metabolic acidosis, or low and high potassium diets. Changes in protein and mRNA levels under these conditions were consistent with a role for KCC3 in glucose resorption and KCC4 in salt reabsorption and acid secretion in the kidney.