Adult growth hormone deficiency (AGHD) is associated with osteoporosis. Previous reports have suggested that alterations in parathyroid gland responsiveness to changes in calcium concentration may play a role in the genesis of osteoporosis in untreated AGHD patients. We investigated the endogenous parathyroid hormone [PTH-(1-84)] response to hypocalcemic and hypercalcemic stimuli induced by sodium EDTA and calcium gluconate infusion, respectively, and to PTH-(1-34) infusion in AGHD patients before and during GH replacement (GHR). We have demonstrated that the maximum PTH-(1-84) stimulation and suppression occurred at significantly higher calcium concentrations and in response to smaller changes in calcium concentrations after GHR. The calcemic response to the effects of PTH-(1-34) infusion significantly increased after GHR. The calcium set point (the calcium concentration at which the rate of PTH secretion is one-half of its maximal value) significantly increased in all groups after 3 mo on GHR, and it increased further at 12 mo. Our results suggest increased parathyroid gland sensitivity to smaller changes in serum calcium and increased end-organ sensitivity to the effects of PTH in AGHD patients after GHR. These findings may help us to understand the mechanisms underlying the genesis of osteoporosis in AGHD patients.