Hypophosphatemia is occasionally observed during total parenteral nutrition (TPN). The phenomenon was recognized since the introduction of TPN and was attributed to preexisting phosphate deficits and inadequate phosphate supplements. Because of the close relationship between phosphate and calcium metabolisms, we speculated that calcium additives may also influence phosphate balance and distribution during TPN. We tested this hypothesis in previously fasted animals receiving TPN with variable amounts of calcium and maintenance or no phosphate. Fasting resulted in considerable losses of phosphate in the urine. Refeeding (with TPN) after fasting produced hypophosphatemia but only in animals receiving calcium additives and no maintenance phosphate in the solution. Addition of moderate or large amounts of calcium decreased phosphate in the muscle in groups not receiving maintenance phosphate. There were no significant changes in bone phosphate. Increasing calcium intake was accompanied by significant and progressive reductions in urine phosphate in animals receiving maintenance phosphate, thus increasing net phosphate retention in those groups. In other respects, refeeding with TPN after fasting displayed features compatible with those of the phosphate depletion syndrome, including hypophosphatemia, hypophosphaturia, hypercalcemia, and hypercalciuria. The magnitude of change in these parameters seemed to be dependent upon the amount of calcium added and the availability of phosphate in the solution.