The optimal dialysate calcium (Ca) content for hemodialysis has been classically fixed at 1.75 mM. However, this dialysate Ca concentration (dCa) with its positive intradialytic Ca balance combined with the use of CaCO3 as a phosphate binder may result in hypercalcemia. To prevent or treat hypercalcemia, a decrease in dCa has been proposed. In the present study both the acute and the long-term effects of lowering dCa were assessed. Additionally, given the results obtained after one year with low dCa the effectiveness of i.v. 1α vitamin D3 in lowering PTH serum levels in two groups of patients dialyzed with different dCa was also studied. (a) Ca kinetics during hemodialysis (HD) and on line hemodiafiltration (HDF) were studied in a group of nine stable patients who were sequentially treated with 1.75, 1.5 and 1.25 mM dCa. Dialysate was the same but for the dCa which was lowered stepwise. Na, K, tCa, ionized Ca (iCa), proteins, phosphate and pH were measured from blood inlet and outlet and dialysate outlet at the start, one hour, two hours and after the treatments. At the same time weight, blood pressure and heart rate were recorded. The sieving of iCa was significantly different in HDF versus HD (F = 6.73; P < 0.01); intravenous infusion of 18 liters of filtered ultrapure dialysate compensated the Ca loss due to the convective component of HDF, as iCa was similar at the blood inlet in HD and HDF in the three dCa tested (F = 2.59; NS). Intradialytic iCa kinetics measured in the blood inlet were significantly different with different dCa (P < 0.001 for 1.75 mM vs. 1.5 mm and P < 0.001 for 1.5 mM vs. 1.25 mM). A significant increase in post-dialysis iCa was observed with dCa of 1.75 and 1.5 while no modification was observed with 1.25 mM dCa. (b) Regarding long-term effects of lowering dCa, seven of the nine ients acutely studied were followed for a one year period after changing from dCa = 1.5 to dCa = 1.25 mM. A control group of six patients was maintained with dCa = 1.5 for the same period of time and with the same treatment schedule but for dCa. Total Ca, phosphate and alkaline phosphatase were assessed monthly, and phosphate binders and oral vitamin D derivative doses were adapted accordingly. Intact PTH was determined quarterly. CaCO3 oral intake was more than doubled in the low dCa group. Total Ca, phosphate and ALP were similar in both groups over the assessed year. However, a significant increase in PTH was observed after one year treatment with 1.25 mM dCa (94 ± 40 vs. 296 ± 99 pg/ml; P < 0.05) which was not observed in the dCa = 1.5 mM control group (92 ± 24 vs. 113 ± 24 pg/ml; NS). (c) For the effects of high-dose i.v. 1α vitamin D3 on PTH serum levels, six of the patients maintained with dCa = 1.25 mM for one year tolerated the treatment with 1α vitamin D3. A control group of six patients dialyzed with dCa = 1.5 mM and with comparable PTH levels was submitted to identical treatment and follow-up. High dose i.v. 1α vitamin D3 resulted in a similar iPTH reduction (72 and 75%; P < 0.0313) in both groups within four months of treatment. This study shows that low dCa can be used both in HD and HDF with no associated clinical intolerance. However, the increase in oral Ca intake was not sufficient to prevent the stimulation of PTH secretion observed with dCa = 1.25 mM. Complementary treatment with high doses of vitamin D derivatives reverses PTH increase both in 1.5 and 1.25 mM dCa treated patients.