The physiologic response to intravenous calcium chloride infusion (12 mueq Ca/min/kg for 1.5 h) was measured in 24 newborn dogs, 4-28 days of age, and in 8 adult dogs for comparison. All adult and 18 of the newborn dogs were thyroparathyroidectomized (TPTX). The other 6 newborn dogs were sham operated as controls. Control puppies had higher plasma calcium, lower plasma phosphate and higher renal phosphate excretion than TPTX puppies indicating effective parathormone function in the newborn. Striking differences in response to calcium infusion between TPTX adults and puppies were reflected by a larger rise in serum calcium and in calcium excretion in adults than in intact or TPTX puppies (p less than 0.01). Moreover, plasma phosphate and renal phosphate excretion rose in the adult and fell in the puppy. 4 TPTX adult dogs and 4 TPTX puppies were volume expanded with saline (33 and 42%, respectively). Compared to the adult, the natriuretic response to expansion in the puppy (fractional sodium excretion, FENa, equaled 2.3%) was significantly (p less than 0.05) less than that of the adult (FENa = 8.5%). The calciuretic response, however, was the same for the adult and newborn (FECa = 12.6 and 10.2%, respectively). These results suggest that in response to calcium infusion, there is a greater deposition of calcium and phosphorus in the bone and other tissues of the newborn animal compared to the adult, accounting for the lower rise in serum calcium, the fall in serum phosphate and the lower renal calcium excretion in the puppy. This response is largely independent of parathyroid hormone or calcitonin. The attenuated natriuretic response and good calciuretric response to saline expansion in the newborn dog are consistent with the hypothesis of a linked proximal tubular calcium and sodium reabsorptive mechanism and an unlinked distal nephron mechanism in the newborn animal.