An increase in the serum calcium level is known to stimulate calcitonin secretion, but whether calcitonin contributes to calcium regulation in the dialysis patient is not known. Because we recently observed in the rat that (1) a sigmoidal calcitonin-calcium curve was present, and (2) calcitonin stimulation decreased the calcemic response to parathyroid hormone (PTH), the relationship between serum calcitonin and calcium was studied in six hemodialysis patients. To evaluate both the calcitonin-calcium and PTH-calcium relationships, hemodialysis with a low-calcium dialysate (2 mg/dL) was performed and followed 1 week later by hemodialysis with a high-calcium dialysate (8 mg/dL). The calcitonin-calcium relationship was best represented as a sigmoidal curve that was opposite in direction to the PTH-calcium curve. The range of the calcitonin-calcium curve was less than the PTH-calcium curve; as a percent of maximal, the minimal calcitonin was higher than the minimal PTH, 61% ± 5% versus 26% ± 4% (P < 0.001). As opposed to the PTH-calcium curve in which the basal PTH value was intermediate between the minimal and maximal PTH, the basal calcitonin value was close to the minimal calcitonin. Despite a wide range of ionized serum calcium concentrations (3.5 to 5.3 mg/dL), maximal stimulation was greater than maximal inhibition of calcitonin, 60% ± 13% versus 3% ± 2% (P = 0.01). Finally, a significant correlation was observed between basal and maximal calcitonin (r = 0.99, P < 0.001). In summary, (1) a sigmoidal calcitonin-calcium curve opposite in direction to the PTH-calcium curve was observed; (2) the range of the calcitonin-calcium curve was less than the PTH-calcium curve; (3) the serum calcium level at which calcitonin was stimulated appeared to be dependent on the basal serum calcium; and (4) the correlation between basal and maximal calcitonin levels suggests that the mass of calcitonin-secreting cells may vary among hemodialysis patients. © 1993, National Kidney Foundation, Inc.. All rights reserved.