BACKGROUND The purpose of this study was to determine if dietary potassium (K) deficiency regulates renal proximal tubular sodium gradient-dependent sulfate transport (Na/Si cotransport) in the rat and, furthermore, determine if the regulation takes place at the level of the recently cloned Na/Si cotransport system (NaSi-1). Methods and Results. Rats treated chronically (seven days) with a K-deficient diet had a significant decrease in serum Si levels and an increase in fractional excretion of ultrafilterable Si, which paralleled a significant decrease in brush border membrane (BBM) Na/Si cotransport activity. The decrease in BBM Na/Si cotransport activity was associated with decreases in BBM NaSi-1 protein and renal cortical NaSi-1 mRNA abundance. In addition, in Xenopus oocytes injected with mRNA from kidney cortex slices of K-deficient rats, there was a significant reduction in the induced Na/Si cotransport, whereas there was no alteration in l-leucine uptake, suggesting that in K-deficient rats, there is a specific decrease in functional mRNA encoding the NaSi-1 mRNA. CONCLUSIONS These findings indicate that chronic K deficiency leads to a reduction in serum Si levels and an increase fractional excretion of Si, and reduces Si reabsorption by down-regulating the expression of the proximal tubular Na/Si-1 cotransporter protein and mRNA.