Serum immunoreactive parathyroid hormone (iPTH), calcium, magnesium, and phosphorus levels were measured in 13 premature infants during the first 96 hours of life. Hypocalcemia at 12-24 hours of age was associated with a markedly elevated mean serum iPTH level. Six of the hypocalcemic infants received a continuous infusion of calcium while seven were not treated. In the untreated infants, the mean serum calcium remained in the hypocalcemic range while the serum iPTH progressively increased. By contrast, the mean serum calcium in the treated infants increased to 2.35 mmol/l at 96 hours of age and was accompanied by a decline in serum iPTH. At 72 and 96 hours, the mean serum iPTH was twofold greater in the untreated than in the treated infants. The results indicate that the parathyroid glands of premature infants respond to calcium signals and that a factor(s), other than parathyroid insufficiency, plays an etiologic role in the hypocalcemia of prematurity.