Calcitonin and acetazolamide inhibit bone resorption in the ureter-ligated rat. Calcitonin treatment results in an ensuing hypocalcemia and hypophosphatemia. Although acetazolamide treatment results in a hypocalcemic response similar to that seen with calcitonin, plasma phosphate concentrations increase or remain unchanged after drug treatment. Data are presented indicating that acetazolamide exhibits two effects that influence blood phosphate. Drug treatment of ureter-ligated rats results in an inhibition of bone resorption which tends to lower blood phosphate concentrations. However, this effect is masked by a drug-induced hypercapnia which results in an increase in plasma phosphate concentrations. Elevation of blood pCO2 also attenuates the hypophosphatemic response to calcitonin.