Calves are born with hypercalcemia which recedes within 2-3 wk. To assess the role of the parathyroids in this condition, immunoreactive parathyroid hormone (iPTH) secretion rate was measured during induced alterations of plasma Ca concentration in 6 anesthetized calves which were 1-3 days of age. The technique involved RIA [radioimmunoassay] of parathyroid venous blood which was collected during timed intervals and measured volumetrically. Elevation of plasma Ca concentration decreased PTH secretion rate but above 12 mg/100 ml, a nonsuppressible rate of secretion was maintained despite any furhter increase in plasma Ca concentration. Between 9.5-12 mg/100 ml, iPTH secretion rate and plasma Ca concentration were inversely related. A maximal rate of secretion was attained when plasma Ca concentration was reduced to 9.5 mg/100 ml, and it did not increase when plasma Ca was reduced to a lower level. The sigmoid relationship between iPTH secretion rate and plasma Ca concentration is similar to that previously described for older calves (2-14 wk of age) except that the sigmoid curve in the neonates is shifted to the right (or toward hypercalcemia) of the curve in the older calves. The plasma Ca concentration, below which large increases in iPTH secretion rate are observed, is set at a higher level in the neonates. Maximal and minimal secretion rates were greater in the neonates than in the older calves. This may have been due to a relatively greater mass of parathyroid tissue in the neonates. Parathyroid hyperactivity, which is indicated by increased parathyroid mass, hypersecretion, and the shift in the secretory response to Ca, together with hypercalcemia, suggests that neonatal hypercalcemia in calves may be a form of hyperparathyroidism. The shift of the secretory response to Ca in the neonate may provide an indication as to the nature of the secretory defect which leads to hypercalcemia in other forms of hyperparathyroidism.