Inorganic sulfate reabsorption was studied during sulfate infusion in guinea pigs stabilized on high-sulfate, normal-sulfate or low-sulfate diets. Guinea pigs stabilized on a low-sulfate diet exhibited 86-91% fractional sulfate reabsorption at normal plasma sulfate concentrations. Fractional renal sulfate reabsorption in animals stabilized on a high-sulfate diet was 55-70%. Clearance techniques were used to determine the glomerular filtration rate and the fractional reabsorption of sulfate during sulfate infusion. Animals fed a high-sulfate diet manifested marked sulfaturia in response to sulfate infusion. The increase in fractional reabsorption associated with decreases in dietary sulfate intake suggests a tubular adaptive mechanism, similar to that demonstrated for phosphate, to increase sulfate reabsorption and maintain constant plasma sulfate concentration. Dietary sulfate-dependent alterations in renal sulfate reabsorption may play a significant role in establishing the rate of sulfate excretion and thus regulating sulfate balance.