Investigations of the effects of calcitriol on the inverse sigmoidal relationship between parathyroid hormone (PTH) and ionized calcium (iCa) have yielded contradictory conclusions, possibly because of variations in experimental and analytical approaches. To clarify the existing literature, PTH-iCa curves were constructed by inducing hypo- and hypercalcemia through alterations in dialysate calcium concentration in eight hemodialysis patients with mild to moderate secondary hyperparathyroidism. The effects of low (metabolic acidosis) versus normal bicarbonate dialysis were compared before and after 4 wk of intravenous calcitriol, in a cross-over design. The PTH-iCa curves were primarily evaluated by using a four-parameter model. In addition, a variety of alternative published analytic approaches were examined and PTH-iCa curve slopes were further evaluated after normalization by (maximum - minimum PTH). The latter partially corrects for gland mass and cell-secretory capacity, and therefore yields a purer measure of the sensitivity of secretory activity to changes in iCa. The results of the study indicate that calcitriol decreased basal, maximal, and minimal PTH and non-normalized slope (all P < 0.05), but did not affect set point or normalized slope, independent of the specific analytic approach. Acute metabolic acidosis did not affect the PTH-iCa curve. Thus, intravenous calcitriol appears to decrease parathyroid gland functional mass, as reflected by decreases in maximal and minimal PTH levels, but does not affect the sensitivity of the parathyroid gland to changes in iCa, as set point and normalized slope were unaffected.