The SAT1 anion exchanger is expressed on basolateral membranes of the renal proximal tubule and the liver and is able to mediate transport of anions such as sulfate, chloride, bicarbonate, or oxalate. In the kidney the transporter has been implicated into the basolateral release of reabsorbed sulfate into blood. We have previously observed in microarray and proteome studies that 2 and 7 days of NH₄Cl-induced acidosis increased SAT1 mRNA and protein in mouse kidney. Here we studied now the in vivo regulation of SAT1 in rat kidney and liver. Rats were given NaCl, Na₂SO₄, NaCl + NH₄Cl, or Na₂SO₄ + NH₄Cl for 7 days to dissect the regulation by acidosis or sulfate repletion/depletion. Addition of NH₄Cl to the diet induced similar metabolic acidosis in both groups with increased urinary acid excretion as expected. NH₄Cl together with NaCl as well as dietary sulfate alone stimulated urinary sulfate excretion. Addition of sulfate to the diet reduced mRNA expression of the renal NaSi (SLC13A1) sulfate transporter but had no effect on renal SAT1 mRNA and protein. NH₄Cl-loading with NaCl reduced NaSi mRNA but did not alter SAT1 mRNA. Combined Na₂SO₄ and NH₄Cl loading decreased NaSi mRNA but again did not affect SAT1 mRNA. In kidney, NH₄Cl treatment enhanced SAT1 protein expression 3-4 fold. In contrast, in liver, Na₂SO₄ or NH₄Cl alone increased SAT1 mRNA whereas the combination of both treatments had surprisingly no effect. Thus, regulation of SAT1 by sulfate and acidosis may be organ-/cell-specific. The exact role of SAT1 in the transport of sulfate and other substrates in both organs requires further elucidation.