The effects of acute hypercalcemia produced by infusing calcium lactate were studied in dogs during hydration and hydropenia. This allowed a direct observation of the effect of calcium on renal concentrating and diluting functions. Both CH2O and TcH2O were consistently reduced and urinary Na excretion increased with acute hypercalcemia. These effects could not be attributed to a reduction in GFR, since inflation of a balloon in the aorta without hypercalcemia reduced GFR to a comparable extent, but did not influence free-water reabsorption. Moreover, hypercalcemia during hypotonic saline diuresis impaired CH2O but did not reduce glomerular filtration rate. It is concluded that hypercalcemia has a direct and immediate effect on the sodium transport mechanism of the thick ascending limb of Henle’s loop, inhibiting Na transport and thereby reducing medullary tonicity. In consequence, free-water reabsorption and free-water formation are diminished and Na excretion increased.