The long-term clinical effects of the use of a low calcium concentration in the dialysate are largely unknown. For this reason, the influence of low-calcium dialysate on parathyroid hormone (PTH) secretion in hemodialysis patients and its long-term effect on the severity of secondary hyperparathyroidism were studied. In 35 hemodialysis patients, the dialysate calcium concentration was lowered from 1.75 to 1.25 mmol/L. Twelve months later, serum iPTH levels increased significantly from 18.6 to 33.2 pmol/L and so did alkaline phosphatase levels, from 210 to 330 IU/L, without significant changes in serum calcium or phosphorus levels. Hemodialysis with low-calcium dialysate (1.25 mmol/L) induced a net calcium loss in 10 patients, without modifications in ionized serum calcium levels. In addition, mean serum iPTH increased 20% over baseline levels, reaching the maximal level at 30 min after the start of hemodialysis with low-calcium dialysate. In contrast, mean serum iPTH levels drop dramatically at 30 min of hemodialysis with high-calcium dialysate (1.75 mmol/L). It was concluded that low-calcium dialysate worsens secondary hyperparathyroidism in hemodialysis patients, probably by inducing a negative calcium balance and causing repetitive stimulation of PTH secretion in each dialysis. The maintenance of normal serum calcium levels could be due to PTH-induced calcium mobilization from bone.