The acute effects on parathyroid gland activity of repetitive hemodialysis with a dialysate calcium concentration of between 3.5 and 4 mEq/l were evaluated in 21 hemodialysis patients on calcitriol therapy for 1 year or more. In this study circulating immunoreactive parathyroid hormone (iPTH) levels were measured using radioimmunoassay specific for C-terminal iPTH (C-PTH), middle molecule iPTH (MM-PTH) and intact iPTH (I-PTH), before the dialysis session at the end of the week (I), after 4 h regular hemodialysis (II) and after a further 72 h (III). C-PTH was abnormally high (202 +/- 64 pmol/l) (I) in 18 patients with no documented parathyroid hyperplasia and showed no significant difference in subsequent controls. MM-PTH was also high (379 +/- 125.5 pmol/l) (I), but decreased to 348 +/- 136.7 (II) (p less than 0.05) and returned to predialysis levels (III). I-PTH (I) was 8.2 +/- 5.3 pmol/l (normal levels in 8 patients), fell to 3.4 +/- 2.6 pmol/l (II) (p less than 0.01), and increased (p less than 0.01) with respect to the basal levels of 11.1 +/- 7.5 pmol/l (III). Three patients presented echographically documentable parathyroid hyperplasia and, despite constantly high iPTH levels, showed a similar I-PTH behavior while MM-PTH and C-PTH revealed no constant pattern. The decrease in iPTH levels was accompanied by a significant increase in total calcium and ionized calcium during the hemodialysis session. No significant changes in iCa and Ca together with I-PTH levels were found in 4 volunteers before and after the hemodialysis session with dialysate calcium 2.75 mEq/l. We conclude that I-PTH assay has been shown to capture acute changes in parathyroid gland activity in hemodialyzed patients for both low and high iPTH levels. High calcium dialysate hemodialysis inhibits acutely intradialytic PTH secretion but the effect is just temporary and the 72-hour interdialytic period, despite vitamin D therapy, stimulates parathyroid secretion significantly. Nevertheless, I-PTH fluctuations occur in some patients within the normal range, and high dialysate and calcitriol therapy seem to be capable of controlling parathyroid activity; as regards the remaining population, we suggest that a personalized therapeutic approach should be studied with a view to achieving a better control of interdialytic calcium homeostasis.