Extracellular Ca++ concentration [Ca++] and parathormone (PTH) are related by a sigmoidal function. The set point of the control system is the [Ca++] that produces a half-maximal inhibition of PTH secretion. Whether or not this set point is abnormal in patients with chronic renal failure (CRF) and secondary hyperparathyroidism (SHP) is controversial.We investigated whether the way [Ca++] is varied [hemodialysis (HD) or calcium gluconate/sodium citrate infusions (INF)] and the way the curve is constructed (four-parameter model or adapted four-parameter, created by Felsenfeld) could influence this set point. We performed dynamic tests of PTH secretion in 12 patients with CRF and SHP during either HD or INF. Both the four-parameter model or adapted four-parameter methods were used, creating four combinations: (a) hypocalcemia and hypercalcemia induced during HD, calculated by Brown's formula (HDB); (b) hypocalcemia and hypercalcemia induced during HD, calculated by Felsenfeld's formula (HDF); (c) hypocalcemia and hypercalcemia induced during infusion, calculated by Brown's formula (INFB); and (d) hypocalcemia and hypercalcemia induced during infusion, calculated by Felsenfeld's formula (INFF).The set points obtained with HDB correlated perfectly with those obtained with HDF (R2 = 0.999). A similar relationship was found between INFB and INFF (R2 = 0.9997). In contrast, there was no correlation between either HDB and INFB (R2 = 0.0157) or HDF and INFF (R2 = 0.0204).These findings indicate that the calculated [Ca++] set point in patients with CRF and SHP is determined by the way [Ca++] is varied, rather than by the mathematical model used to generate the curves. Further studies are needed to determine the differing physiological mechanisms triggered by HD and INF and the way they influence [Ca++] homeostasis in this setting.