Changes in plasma calcium and 45Ca concentrations were followed after injection of calcitonin or a combination of calcitonin (CT) and parathyroid hormone (PTH) into thyroparathyroidectomized rats maintained on thyroxine. Comparison was made between rats injected with the hormone(s) after a recent feeding and after an overnight fast. Also cor (18 hr 45Ca) before, and more than 6 days (greater than 6 day 45Ca) prior to hormone administration. The following results were obtained: The action of CT predominated over that of PTH for the first few hours after injection. However, the effects of PTH were eventually manifested even when additional CT was administered. In the "greater than 6 day" 45Ca groups, PTH normally produced an increase in plasma 45Ca specific activity. However, in fasted rats, plasms 45Ca fell with total calcium with no change in specific activity following CT injection. In fed rats CT injection was followed by a decrease in plasma 45Ca specific activity. When both hormones were administered plasma 45Ca specific activity changes mimicked those produced by CT alone even after PTH plasma effects were manifested. In the "18 hr" 45Ca groups, CT produced first a drop in plasma 45Ca, followed by a reduction in the rate of its removal from plasma. It is concluded that the data can best be explained by the postulate that plasma calcium concentrations are maintained by the control of fluxes between bone fluid in the osteocyte-lining cell bone unit and the extracellular fluid. PTH increases the efflux from this bone fluid compartment while CT restricuts the source of calcium and, therefore, the efflux. Plasma 45Ca changes are due to a combination of changes in flux rates and mixing processes between the extracellular fluid compartment and the bone fluid compartment.