Constant intravenous infusion (65 to 260 ng/min) of prostaglandin E2 (PGE2) produced an elevation of the plasma calcium concentration in unanesthetized rats in a period of 4 h. The increase in plasma calcium was related to the amount of PGE2 infused, and the hypercalcemia persisted for at least 10 h during continuous infusion. There was also a small increase in plasma inorganic phosphorus concentration. The increase in plasma calcium was not due to hemoconcentration; in fact, there was a small decrease in hematocrit during infusion of PGE2, and no change in total plasma protein concentration was detected. Infusion of PGF2, did not raise plasma calcium concentration. We conclude that under appropriate conditions, the exogenous administration of PGE2 can cause an elevation of plasma calcium in the intact rat.